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Dendritic Cells in the Immune System—History, Lineages, Tissues, Tolerance, and Immunity

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  • Author: Jonathan M. Austyn1
  • Editor: Siamon Gordon2
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom; 2: Oxford University, Oxford, United Kingdom
  • Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0046-2016
  • Received 01 August 2016 Accepted 22 September 2016 Published 02 December 2016
  • Jonathan M. Austyn, jon.austyn@nds.ox.ac.uk
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  • Abstract:

    The aim of this review is to provide a coherent framework for understanding dendritic cells (DCs). It has seven sections. The introduction provides an overview of the immune system and essential concepts, particularly for the nonspecialist reader. Next, the “History” section outlines the early evolution of ideas about DCs and highlights some sources of confusion that still exist today. The “Lineages” section then focuses on five different populations of DCs: two subsets of “classical” DCs, plasmacytoid DCs, monocyte-derived DCs, and Langerhans cells. It highlights some cellular and molecular specializations of each, and also notes other DC subsets that have been proposed. The following “Tissues” section discusses the distribution and behavior of different DC subsets within nonlymphoid and secondary lymphoid tissues that are connected by DC migration pathways between them. In the “Tolerance” section, the role of DCs in central and peripheral tolerance is considered, including their ability to drive the differentiation of different populations of regulatory T cells. In contrast, the “Immunity” section considers the roles of DCs in sensing of infection and tissue damage, the initiation of primary responses, the T-cell effector phase, and the induction of immunological memory. The concluding section provides some speculative ideas about the evolution of DCs. It also revisits earlier concepts of generation of diversity and clonal selection in terms of DCs driving the evolution of T-cell responses. Throughout, this review highlights certain areas of uncertainty and suggests some avenues for future investigation.

  • Citation: Austyn J. 2016. Dendritic Cells in the Immune System—History, Lineages, Tissues, Tolerance, and Immunity. Microbiol Spectrum 4(6):MCHD-0046-2016. doi:10.1128/microbiolspec.MCHD-0046-2016.

Key Concept Ranking

Adaptive Immune System
0.8541004
Innate Immune System
0.83345234
Complement System
0.78173226
Infection and Immunity
0.6685628
Immune Systems
0.66052437
Major Histocompatibility Complex
0.5694128
0.8541004

References

1. Sompayrak L. 2016. How the Immune System Works, 5th ed. John Wiley & Sons, Chichester, United Kingdom.
2. MacPherson GG, Austyn JM. 2012. Exploring Immunology: Concepts and Evidence, 1st ed. Wiley-VCH Verlag, Weinheim, Germany.
3. Murphy KM, Weaver CT. 2016. Janeway’s Immunobiology, 9th ed. Garland Science, Taylor & Francis Group, New York, NY.
4. Paul WE (ed). 2013. Fundamental Immunology, 7th ed. Lippincott Williams & Wilkins, Philadelphia, PA.
5. Flajnik MF, Du Pasquier L. 2013. Evolution of the immune system, p 67–128. In Paul WE (ed), Fundamental Immunology, 7th ed. Lippincott Williams & Wilkins, Philadelphia, PA.
6. Sewell AK. 2012. Why must T cells be cross-reactive? Nat Rev Immunol 12:669–677. [PubMed]
7. Steinman RM, Cohn ZA. 1973. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 137:1142–1162. [PubMed]
8. Zinkernagel RM, Doherty PC. 1974. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature 248:701–702. [PubMed]
9. Steinman RM, Witmer MD. 1978. Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice. Proc Natl Acad Sci U S A 75:5132–5136.
10. Farrant J, Clark JC, Lee H, Knight SC, O’Brien J. 1980. Conditions for measuring DNA synthesis in PHA stimulated human lymphocytes in 20 microliters hanging drops with various cell concentrations and periods of culture. J Immunol Methods 33:301–312.
11. Inaba K, Steinman RM, Van Voorhis WC, Muramatsu S. 1983. Dendritic cells are critical accessory cells for thymus-dependent antibody responses in mouse and in man. Proc Natl Acad Sci U S A 80:6041–6045. [PubMed]
12. Austyn JM, Steinman RM, Weinstein DE, Granelli-Piperno A, Palladino MA. 1983. Dendritic cells initiate a two-stage mechanism for T lymphocyte proliferation. J Exp Med 157:1101–1115. [PubMed]
13. Macatonia SE, Hosken NA, Litton M, Vieira P, Hsieh CS, Culpepper JA, Wysocka M, Trinchieri G, Murphy KM, O’Garra A. 1995. Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. J Immunol 154:5071–5079. [PubMed]
14. Veldman JE, Molenaar I, Keuning FJ. 1978. Electron microscopy of cellular immunity reactions in B-cell deprived rabbits. Thymus derived antigen reactive cells, their micro-environment and progeny in the lymph node. Virchows Arch B Cell Pathol 28:217–228.
15. Veerman AJ. 1974. On the interdigitating cells in the thymus-dependent area of the rat spleen: a relation between the mononuclear phagocyte system and T-lymphocytes. Cell Tissue Res 148:247–257. [PubMed]
16. Balfour BM, Drexhage HA, Kamperdijk EW, Hoefsmit EC. 1981. Antigen-presenting cells, including Langerhans cells, veiled cells and interdigitating cells. Ciba Found Symp 84:281–301. [PubMed]
17. Metlay JP, Witmer-Pack MD, Agger R, Crowley MT, Lawless D, Steinman RM. 1990. The distinct leukocyte integrins of mouse spleen dendritic cells as identified with new hamster monoclonal antibodies. J Exp Med 171:1753–1771. [PubMed]
18. Köhler G, Milstein C. 1975. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497. [PubMed]
19. Crowley M, Inaba K, Witmer-Pack M, Steinman RM. 1989. The cell surface of mouse dendritic cells: FACS analyses of dendritic cells from different tissues including thymus. Cell Immunol 118:108–125. [PubMed]
20. Landry D, Lafontaine M, Cossette M, Barthélémy H, Chartrand C, Montplaisir S, Pelletier M. 1988. Human thymic dendritic cells. Characterization, isolation and functional assays. Immunology 65:135–142. [PubMed]
21. Inaba K, Hosono M, Inaba M. 1990. Thymic dendritic cells and B cells: isolation and function. Int Rev Immunol 6:117–126. [PubMed]
22. Schuler G, Romani N, Steinman RM. 1985. A comparison of murine epidermal Langerhans cells with spleen dendritic cells. J Invest Dermatol 85(Suppl):99s–106s. [PubMed]
23. Schuler G, Steinman RM. 1985. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J Exp Med 161:526–546. [PubMed]
24. Reis e Sousa C, Stahl PD, Austyn JM. 1993. Phagocytosis of antigens by Langerhans cells in vitro. J Exp Med 178:509–519. [PubMed]
25. Hart DN, Fabre JW. 1981. Demonstration and characterization of Ia-positive dendritic cells in the interstitial connective tissues of rat heart and other tissues, but not brain. J Exp Med 154:347–361. [PubMed]
26. Hart DN, McKenzie JL. 1990. Interstitial dendritic cells. Int Rev Immunol 6:127–138. [PubMed]
27. Austyn JM, Hankins DF, Larsen CP, Morris PJ, Rao AS, Roake JA. 1994. Isolation and characterization of dendritic cells from mouse heart and kidney. J Immunol 152:2401–2410. [PubMed]
28. Steinman RM, Pack M, Inaba K. 1997. Dendritic cells in the T-cell areas of lymphoid organs. Immunol Rev 156:25–37. [PubMed]
29. Milling S, Yrlid U, Cerovic V, MacPherson G. 2010. Subsets of migrating intestinal dendritic cells. Immunol Rev 234:259–267. [PubMed]
30. Mason DW, Pugh CW, Webb M. 1981. The rat mixed lymphocyte reaction: roles of a dendritic cell in intestinal lymph and T-cell subsets defined by monoclonal antibodies. Immunology 44:75–87. [PubMed]
31. Spry CJ, Pflug AJ, Janossy G, Humphrey JH. 1980. Large mononuclear (veiled) cells like ‘Ia-like’ membrane antigens in human afferent lymph. Clin Exp Immunol 39:750–755. [PubMed]
32. Drexhage HA, Mullink H, de Groot J, Clarke J, Balfour BM. 1979. A study of cells present in peripheral lymph of pigs with special reference to a type of cell resembling the Langerhans cell. Cell Tissue Res 202:407–430. [PubMed]
33. Thorbecke GJ, Silberberg-Sinakin I, Flotte TJ. 1980. Langerhans cells as macrophages in skin and lymphoid organs. J Invest Dermatol 75:32–43. [PubMed]
34. Knight SC, Balfour BM, O’Brien J, Buttifant L, Sumerska T, Clarke J. 1982. Role of veiled cells in lymphocyte activation. Eur J Immunol 12:1057–1060. [PubMed]
35. Larsen CP, Steinman RM, Witmer-Pack M, Hankins DF, Morris PJ, Austyn JM. 1990. Migration and maturation of Langerhans cells in skin transplants and explants. J Exp Med 172:1483–1493. [PubMed]
36. Stoitzner P, Pfaller K, Stössel H, Romani N. 2002. A close-up view of migrating Langerhans cells in the skin. J Invest Dermatol 118:117–125. [PubMed]
37. O’Doherty U, Peng M, Gezelter S, Swiggard WJ, Betjes M, Bhardwaj N, Steinman RM. 1994. Human blood contains two subsets of dendritic cells, one immunologically mature and the other immature. Immunology 82:487–493. [PubMed]
38. Kupiec-Weglinski JW, Austyn JM, Morris PJ. 1988. Migration patterns of dendritic cells in the mouse. Traffic from the blood, and T cell-dependent and -independent entry to lymphoid tissues. J Exp Med 167:632–645. [PubMed]
39. Austyn JM, Kupiec-Weglinski JW, Hankins DF, Morris PJ. 1988. Migration patterns of dendritic cells in the mouse. Homing to T cell-dependent areas of spleen, and binding within marginal zone. J Exp Med 167:646–651.
40. Larsen CP, Morris PJ, Austyn JM. 1990. Migration of dendritic leukocytes from cardiac allografts into host spleens. A novel pathway for initiation of rejection. J Exp Med 171:307–314. [PubMed]
41. Cumberbatch M, Dearman RJ, Kimber I. 1997. Interleukin 1 beta and the stimulation of Langerhans cell migration: comparisons with tumour necrosis factor alpha. Arch Dermatol Res 289:277–284. [PubMed]
42. Kimber I, Cumberbatch M. 1992. Stimulation of Langerhans cell migration by tumor necrosis factor alpha (TNF-alpha). J Invest Dermatol 99:48S–50S. [PubMed]
43. Roake JA, Rao AS, Morris PJ, Larsen CP, Hankins DF, Austyn JM. 1995. Dendritic cell loss from nonlymphoid tissues after systemic administration of lipopolysaccharide, tumor necrosis factor, and interleukin 1. J Exp Med 181:2237–2247. [PubMed]
44. Bowers WE, Berkowitz MR. 1986. Differentiation of dendritic cells in cultures of rat bone marrow cells. J Exp Med 163:872–883. [PubMed]
45. Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S, Muramatsu S, Steinman RM. 1992. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med 176:1693–1702. [PubMed]
46. Caux C, Dezutter-Dambuyant C, Schmitt D, Banchereau J. 1992. GM-CSF and TNF-α cooperate in the generation of dendritic Langerhans cells. Nature 360:258–261. [PubMed]
47. Siena S, Di Nicola M, Bregni M, Mortarini R, Anichini A, Lombardi L, Ravagnani F, Parmiani G, Gianni AM. 1995. Massive ex vivo generation of functional dendritic cells from mobilized CD34+ blood progenitors for anticancer therapy. Exp Hematol 23:1463–1471. [PubMed]
48. O’Doherty U, Ignatius R, Bhardwaj N, Pope M. 1997. Generation of monocyte-derived dendritic cells from precursors in rhesus macaque blood. J Immunol Methods 207:185–194. [PubMed]
49. Sallusto F, Lanzavecchia A. 1994. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor α. J Exp Med 179:1109–1118. [PubMed]
50. Romani N, Reider D, Heuer M, Ebner S, Kämpgen E, Eibl B, Niederwieser D, Schuler G. 1996. Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability. J Immunol Methods 196:137–151.
51. Peters JH, Ruhl S, Friedrichs D. 1987. Veiled accessory cells deduced from monocytes. Immunobiology 176:154–166. [PubMed]
52. Palucka K, Banchereau J. 2012. Cancer immunotherapy via dendritic cells. Nat Rev Cancer 12:265–277. [PubMed]
53. Elster JD, Krishnadas DK, Lucas KG. 2016. Dendritic cell vaccines: a review of recent developments and their potential pediatric application. Hum Vaccin Immunother 12:2232–2239. [PubMed]
54. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF, IMPACT Study Investigators. 2010. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363:411–422. [PubMed]
55. Grouard G, Rissoan MC, Filgueira L, Durand I, Banchereau J, Liu YJ. 1997. The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand. J Exp Med 185:1101–1111. [PubMed]
56. Huang FP, Platt N, Wykes M, Major JR, Powell TJ, Jenkins CD, MacPherson GG. 2000. A discrete subpopulation of dendritic cells transports apoptotic intestinal epithelial cells to T cell areas of mesenteric lymph nodes. J Exp Med 191:435–444. [PubMed]
57. Tew JG, Phipps RP, Mandel TE. 1980. The maintenance and regulation of the humoral immune response: persisting antigen and the role of follicular antigen-binding dendritic cells as accessory cells. Immunol Rev 53:175–201. [PubMed]
58. Aguzzi A, Kranich J, Krautler NJ. 2014. Follicular dendritic cells: origin, phenotype, and function in health and disease. Trends Immunol 35:105–113. [PubMed]
59. Chen LL, Adams JC, Steinman RM. 1978. Anatomy of germinal centers in mouse spleen, with special reference to “follicular dendritic cells.” J Cell Biol 77:148–164. [PubMed]
60. Heesters BA, Myers RC, Carroll MC. 2014. Follicular dendritic cells: dynamic antigen libraries. Nat Rev Immunol 14:495–504. [PubMed]
61. Pulendran B. 2015. The varieties of immunological experience: of pathogens, stress, and dendritic cells. Annu Rev Immunol 33:563–606. [PubMed]
62. Merad M, Sathe P, Helft J, Miller J, Mortha A. 2013. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol 31:563–604. [PubMed]
63. Miller JC, Brown BD, Shay T, Gautier EL, Jojic V, Cohain A, Pandey G, Leboeuf M, Elpek KG, Helft J, Hashimoto D, Chow A, Price J, Greter M, Bogunovic M, Bellemare-Pelletier A, Frenette PS, Randolph GJ, Turley SJ, Merad M, Immunological Genome Consortium. 2012. Deciphering the transcriptional network of the dendritic cell lineage. Nat Immunol 13:888–899. [PubMed]
64. Schraml BU, Reis e Sousa C. 2015. Defining dendritic cells. Curr Opin Immunol 32:13–20. [PubMed]
65. Reizis B, Bunin A, Ghosh HS, Lewis KL, Sisirak V. 2011. Plasmacytoid dendritic cells: recent progress and open questions. Annu Rev Immunol 29:163–183. [PubMed]
66. Ginhoux F, Merad M. 2010. Ontogeny and homeostasis of Langerhans cells. Immunol Cell Biol 88:387–392. [PubMed]
67. Guilliams M, Ginhoux F, Jakubzick C, Naik SH, Onai N, Schraml BU, Segura E, Tussiwand R, Yona S. 2014. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat Rev Immunol 14:571–578. [PubMed]
68. De Kleer I, Willems F, Lambrecht B, Goriely S. 2014. Ontogeny of myeloid cells. Front Immunol 5:423. doi:10.3389/fimmu.2014.00423. [PubMed]
69. Lee J, Breton G, Oliveira TYK, Zhou YJ, Aljoufi A, Puhr S, Cameron MJ, Sékaly RP, Nussenzweig MC, Liu K. 2015. Restricted dendritic cell and monocyte progenitors in human cord blood and bone marrow. J Exp Med 212:385–399. [PubMed]
70. Strobl H, Bello-Fernandez C, Riedl E, Pickl WF, Majdic O, Lyman SD, Knapp W. 1997. flt3 ligand in cooperation with transforming growth factor-β1 potentiates in vitro development of Langerhans-type dendritic cells and allows single-cell dendritic cell cluster formation under serum-free conditions. Blood 90:1425–1434. [PubMed]
71. Guo X, Zhou Y, Wu T, Zhu X, Lai W, Wu L. 2016. Generation of mouse and human dendritic cells in vitro. J Immunol Methods 432:24–29. [PubMed]
72. Helft J, Böttcher J, Chakravarty P, Zelenay S, Huotari J, Schraml BU, Goubau D, Reis e Sousa C. 2015. GM-CSF mouse bone marrow cultures comprise a heterogeneous population of CD11c+MHCII+ macrophages and dendritic cells. Immunity 42:1197–1211. [PubMed]
73. Poltorak MP, Schraml BU. 2015. Fate mapping of dendritic cells. Front Immunol 6:199. doi:10.3389/fimmu.2015.00199. [PubMed]
74. Bar-On L, Jung S. 2010. Defining dendritic cells by conditional and constitutive cell ablation. Immunol Rev 234:76–89. [PubMed]
75. Bennett CL, Clausen BE. 2007. DC ablation in mice: promises, pitfalls, and challenges. Trends Immunol 28:525–531. [PubMed]
76. Collin M, Bigley V, Haniffa M, Hambleton S. 2011. Human dendritic cell deficiency: the missing ID? Nat Rev Immunol 11:575–583. [PubMed]
77. Liu K, Victora GD, Schwickert TA, Guermonprez P, Meredith MM, Yao K, Chu F-F, Randolph GJ, Rudensky AY, Nussenzweig M. 2009. In vivo analysis of dendritic cell development and homeostasis. Science 324:392–397. [PubMed]
78. Sathe P, Metcalf D, Vremec D, Naik SH, Langdon WY, Huntington ND, Wu L, Shortman K. 2014. Lymphoid tissue and plasmacytoid dendritic cells and macrophages do not share a common macrophage-dendritic cell-restricted progenitor. Immunity 41:104–115. [PubMed]
79. Murphy TL, Grajales-Reyes GE, Wu X, Tussiwand R, Briseño CG, Iwata A, Kretzer NM, Durai V, Murphy KM. 2016. Transcriptional control of dendritic cell development. Annu Rev Immunol 34:93–119. [PubMed]
80. Naik SH, Perié L, Swart E, Gerlach C, van Rooij N, de Boer RJ, Schumacher TN. 2013. Diverse and heritable lineage imprinting of early haematopoietic progenitors. Nature 496:229–232. [PubMed]
81. Liu K, Nussenzweig MC. 2013. Dendritic cells, p 381–384. In Paul WE (ed), Fundamental Immunology, 7th ed. Lippincott Williams & Wilkins, Philadelphia, PA.
82. Robbins SH, Walzer T, Dembélé D, Thibault C, Defays A, Bessou G, Xu H, Vivier E, Sellars M, Pierre P, Sharp FR, Chan S, Kastner P, Dalod M. 2008. Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profiling. Genome Biol 9:R17. doi:10.1186/gb-2008-9-1-r17.
83. Crozat K, Guiton R, Guilliams M, Henri S, Baranek T, Schwartz-Cornil I, Malissen B, Dalod M. 2010. Comparative genomics as a tool to reveal functional equivalences between human and mouse dendritic cell subsets. Immunol Rev 234:177–198. [PubMed]
84. Granja AG, Leal E, Pignatelli J, Castro R, Abós B, Kato G, Fischer U, Tafalla C. 2015. Identification of teleost skin CD8α+ dendritic-like cells, representing a potential common ancestor for mammalian cross-presenting dendritic cells. J Immunol 195:1825–1837. [PubMed]
85. Rumfelt LL, McKinney EC, Taylor E, Flajnik MF. 2002. The development of primary and secondary lymphoid tissues in the nurse shark Ginglymostoma cirratum: B-cell zones precede dendritic cell immigration and T-cell zone formation during ontogeny of the spleen. Scand J Immunol 56:130–148. [PubMed]
86. García Barrutia MS, Villena A, Gomariz RP, Razquin B, Zapata A. 1985. Ultrastructural changes in the spleen of the natterjack, Bufo calamita, after antigenic stimulation. Cell Tissue Res 239:435–441. [PubMed]
87. Bogunovic M, Ginhoux F, Helft J, Shang L, Hashimoto D, Greter M, Liu K, Jakubzick C, Ingersoll MA, Leboeuf M, Stanley ER, Nussenzweig M, Lira SA, Randolph GJ, Merad M. 2009. Origin of the lamina propria dendritic cell network. Immunity 31:513–525. [PubMed]
88. Hammer GE, Ma A. 2013. Molecular control of steady-state dendritic cell maturation and immune homeostasis. Annu Rev Immunol 31:743–791. [PubMed]
89. Jiao Z, Bedoui S, Brady JL, Walter A, Chopin M, Carrington EM, Sutherland RM, Nutt SL, Zhang Y, Ko H-J, Wu L, Lew AM, Zhan Y. 2014. The closely related CD103+ dendritic cells (DCs) and lymphoid-resident CD8+ DCs differ in their inflammatory functions. PLoS One 9:e91126. doi:10.1371/journal.pone.0091126.
90. Li C, Buckwalter MR, Basu S, Garg M, Chang J, Srivastava PK. 2012. Dendritic cells sequester antigenic epitopes for prolonged periods in the absence of antigen-encoding genetic information. Proc Natl Acad Sci U S A 109:17543–17548. [PubMed]
91. Randolph GJ, Ochando J, Partida-Sánchez S. 2008. Migration of dendritic cell subsets and their precursors. Annu Rev Immunol 26:293–316. [PubMed]
92. Sánchez-Sánchez N, Riol-Blanco L, Rodríguez-Fernández JL. 2006. The multiple personalities of the chemokine receptor CCR7 in dendritic cells. J Immunol 176:5153–5159. [PubMed]
93. Ohl L, Mohaupt M, Czeloth N, Hintzen G, Kiafard Z, Zwirner J, Blankenstein T, Henning G, Förster R. 2004. CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions. Immunity 21:279–288. [PubMed]
94. Smith TRF, Kumar V. 2008. Revival of CD8+ Treg-mediated suppression. Trends Immunol 29:337–342. [PubMed]
95. Dzionek A, Fuchs A, Schmidt P, Cremer S, Zysk M, Miltenyi S, Buck DW, Schmitz J. 2000. BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood. J Immunol 165:6037–6046. [PubMed]
96. Adams TE, Huntington JA. 2006. Thrombin-cofactor interactions: structural insights into regulatory mechanisms. Arterioscler Thromb Vasc Biol 26:1738–1745. [PubMed]
97. Chistiakov DA, Sobenin IA, Orekhov AN, Bobryshev YV. 2015. Myeloid dendritic cells: development, functions, and role in atherosclerotic inflammation. Immunobiology 220:833–844. [PubMed]
98. Uematsu S, Fujimoto K, Jang MH, Yang B-G, Jung Y-J, Nishiyama M, Sato S, Tsujimura T, Yamamoto M, Yokota Y, Kiyono H, Miyasaka M, Ishii KJ, Akira S. 2008. Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Nat Immunol 9:769–776. [PubMed]
99. Iyoda T, Shimoyama S, Liu K, Omatsu Y, Akiyama Y, Maeda Y, Takahara K, Steinman RM, Inaba K. 2002. The CD8+ dendritic cell subset selectively endocytoses dying cells in culture and in vivo. J Exp Med 195:1289–1302. [PubMed]
100. Savill J, Hogg N, Ren Y, Haslett C. 1992. Thrombospondin cooperates with CD36 and the vitronectin receptor in macrophage recognition of neutrophils undergoing apoptosis. J Clin Invest 90:1513–1522. [PubMed]
101. Urban BC, Willcox N, Roberts DJ. 2001. A role for CD36 in the regulation of dendritic cell function. Proc Natl Acad Sci U S A 98:8750–8755. [PubMed]
102. Hanč P, Fujii T, Iborra S, Yamada Y, Huotari J, Schulz O, Ahrens S, Kjær S, Way M, Sancho D, Namba K, Reis e Sousa C. 2015. Structure of the complex of F-actin and DNGR-1, a C-type lectin receptor involved in dendritic cell cross-presentation of dead cell-associated antigens. Immunity 42:839–849. [PubMed]
103. Cao L, Shi X, Chang H, Zhang Q, He Y. 2015. pH-dependent recognition of apoptotic and necrotic cells by the human dendritic cell receptor DEC205. Proc Natl Acad Sci U S A 112:7237–7242. [PubMed]
104. Kim TS, Gorski SA, Hahn S, Murphy KM, Braciale TJ. 2014. Distinct dendritic cell subsets dictate the fate decision between effector and memory CD8+ T cell differentiation by a CD24-dependent mechanism. Immunity 40:400–413. [PubMed]
105. Dudziak D, Kamphorst AO, Heidkamp GF, Buchholz VR, Trumpfheller C, Yamazaki S, Cheong C, Liu K, Lee H-W, Park CG, Steinman RM, Nussenzweig MC. 2007. Differential antigen processing by dendritic cell subsets in vivo. Science 315:107–111. [PubMed]
106. Ohta T, Sugiyama M, Hemmi H, Yamazaki C, Okura S, Sasaki I, Fukuda Y, Orimo T, Ishii KJ, Hoshino K, Ginhoux F, Kaisho T. 2016. Crucial roles of XCR1-expressing dendritic cells and the XCR1-XCL1 chemokine axis in intestinal immune homeostasis. Sci Rep 6:23505. doi:10.1038/srep23505. [PubMed]
107. Lei Y, Ripen AM, Ishimaru N, Ohigashi I, Nagasawa T, Jeker LT, Bösl MR, Holländer GA, Hayashi Y, Malefyt RW, Nitta T, Takahama Y. 2011. Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development. J Exp Med 208:383–394. [PubMed]
108. Guilliams M, Bruhns P, Saeys Y, Hammad H, Lambrecht BN. 2014. The function of Fcγ receptors in dendritic cells and macrophages. Nat Rev Immunol 14:94–108. [PubMed]
109. Atif SM, Uematsu S, Akira S, McSorley SJ. 2014. CD103CD11b+ dendritic cells regulate the sensitivity of CD4 T-cell responses to bacterial flagellin. Mucosal Immunol 7:68–77. [PubMed]
110. Iwasaki A, Medzhitov R. 2015. Control of adaptive immunity by the innate immune system. Nat Immunol 16:343–353. [PubMed]
111. Uto T, Fukaya T, Takagi H, Arimura K, Nakamura T, Kojima N, Malissen B, Sato K. 2016. Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T-cell immunity. Nat Commun 7:11273. doi:10.1038/ncomms11273. [PubMed]
112. Vander Lugt B, Khan AA, Hackney JA, Agrawal S, Lesch J, Zhou M, Lee WP, Park S, Xu M, DeVoss J, Spooner CJ, Chalouni C, Delamarre L, Mellman I, Singh H. 2014. Transcriptional programming of dendritic cells for enhanced MHC class II antigen presentation. Nat Immunol 15:161–167. [PubMed]
113. Persson EK, Uronen-Hansson H, Semmrich M, Rivollier A, Hägerbrand K, Marsal J, Gudjonsson S, Håkansson U, Reizis B, Kotarsky K, Agace WW. 2013. IRF4 transcription-factor-dependent CD103+CD11b+ dendritic cells drive mucosal T helper 17 cell differentiation. Immunity 38:958–969. [PubMed]
114. Swiecki M, Colonna M. 2015. The multifaceted biology of plasmacytoid dendritic cells. Nat Rev Immunol 15:471–485. [PubMed]
115. Reizis B, Colonna M, Trinchieri G, Barrat F, Gilliet M. 2011. Plasmacytoid dendritic cells: one-trick ponies or workhorses of the immune system? Nat Rev Immunol 11:558–565. [PubMed]
116. Shigematsu H, Reizis B, Iwasaki H, Mizuno S, Hu D, Traver D, Leder P, Sakaguchi N, Akashi K. 2004. Plasmacytoid dendritic cells activate lymphoid-specific genetic programs irrespective of their cellular origin. Immunity 21:43–53. [PubMed]
117. Tian J, Avalos AM, Mao SY, Chen B, Senthil K, Wu H, Parroche P, Drabic S, Golenbock D, Sirois C, Hua J, An LL, Audoly L, La Rosa G, Bierhaus A, Naworth P, Marshak-Rothstein A, Crow MK, Fitzgerald KA, Latz E, Kiener PA, Coyle AJ. 2007. Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol 8:487–496. [PubMed]
118. Gregorio J, Meller S, Conrad C, Di Nardo A, Homey B, Lauerma A, Arai N, Gallo RL, Digiovanni J, Gilliet M. 2010. Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons. J Exp Med 207:2921–2930. [PubMed]
119. Cao W, Rosen DB, Ito T, Bover L, Bao M, Watanabe G, Yao Z, Zhang L, Lanier LL, Liu YJ. 2006. Plasmacytoid dendritic cell-specific receptor ILT7-FcεRIγ inhibits Toll-like receptor-induced interferon production. J Exp Med 203:1399–1405. [PubMed]
120. Simmons DP, Wearsch PA, Canaday DH, Meyerson HJ, Liu YC, Wang Y, Boom WH, Harding CV. 2012. Type I IFN drives a distinctive dendritic cell maturation phenotype that allows continued class II MHC synthesis and antigen processing. J Immunol 188:3116–3126. [PubMed]
121. Watowich SS, Liu YJ. 2010. Mechanisms regulating dendritic cell specification and development. Immunol Rev 238:76–92. [PubMed]
122. Guéry L, Hugues S. 2013. Tolerogenic and activatory plasmacytoid dendritic cells in autoimmunity. Front Immunol 4:59. doi:10.3389/fimmu.2013.00059. [PubMed]
123. Cervantes-Barragan L, Lewis KL, Firner S, Thiel V, Hugues S, Reith W, Ludewig B, Reizis B. 2012. Plasmacytoid dendritic cells control T-cell response to chronic viral infection. Proc Natl Acad Sci U S A 109:3012–3017. [PubMed]
124. Jakubzick C, Gautier EL, Gibbings SL, Sojka DK, Schlitzer A, Johnson TE, Ivanov S, Duan Q, Bala S, Condon T, van Rooijen N, Grainger JR, Belkaid Y, Ma’ayan A, Riches DWH, Yokoyama WM, Ginhoux F, Henson PM, Randolph GJ. 2013. Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes. Immunity 39:599–610. [PubMed]
125. Ensan S, Li A, Besla R, Degousee N, Cosme J, Roufaiel M, Shikatani EA, El-Maklizi M, Williams JW, Robins L, Li C, Lewis B, Yun TJ, Lee JS, Wieghofer P, Khattar R, Farrokhi K, Byrne J, Ouzounian M, Zavitz CCJ, Levy GA, Bauer CMT, Libby P, Husain M, Swirski FK, Cheong C, Prinz M, Hilgendorf I, Randolph GJ, Epelman S, Gramolini AO, Cybulsky MI, Rubin BB, Robbins CS. 2016. Self-renewing resident arterial macrophages arise from embryonic CX3CR1+ precursors and circulating monocytes immediately after birth. Nat Immunol 17:159–168. [PubMed]
126. Jung S, Aliberti J, Graemmel P, Sunshine MJ, Kreutzberg GW, Sher A, Littman DR. 2000. Analysis of fractalkine receptor CX3CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol Cell Biol 20:4106–4114. [PubMed]
127. Austyn JM, Gordon S. 1981. F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol 11:805–815. [PubMed]
128. Lin HH, Stacey M, Stein-Streilein J, Gordon S. 2010. F4/80: the macrophage-specific adhesion-GPCR and its role in immunoregulation. Adv Exp Med Biol 706:149–156. [PubMed]
129. Tamoutounour S, Guilliams M, Montanana Sanchis F, Liu H, Terhorst D, Malosse C, Pollet E, Ardouin L, Luche H, Sanchez C, Dalod M, Malissen B, Henri S. 2013. Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. Immunity 39:925–938. [PubMed]
130. Geissmann F, Jung S, Littman DR. 2003. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19:71–82. [PubMed]
131. Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K. 2010. Development of monocytes, macrophages, and dendritic cells. Science 327:656–661. [PubMed]
132. Schlitzer A, McGovern N, Ginhoux F. 2015. Dendritic cells and monocyte-derived cells: two complementary and integrated functional systems. Semin Cell Dev Biol 41:9–22. [PubMed]
133. Espinosa V, Jhingran A, Dutta O, Kasahara S, Donnelly R, Du P, Rosenfeld J, Leiner I, Chen C-C, Ron Y, Hohl TM, Rivera A. 2014. Inflammatory monocytes orchestrate innate antifungal immunity in the lung. PLoS Pathog 10:e1003940. doi:10.1371/journal.ppat.1003940. [PubMed]
134. Lauvau G, Loke P, Hohl TM. 2015. Monocyte-mediated defense against bacteria, fungi, and parasites. Semin Immunol 27:397–409. [PubMed]
135. Hohl TM, Rivera A, Lipuma L, Gallegos A, Shi C, Mack M, Pamer EG. 2009. Inflammatory monocytes facilitate adaptive CD4 T cell responses during respiratory fungal infection. Cell Host Microbe 6:470–481. [PubMed]
136. Plantinga M, Guilliams M, Vanheerswynghels M, Deswarte K, Branco-Madeira F, Toussaint W, Vanhoutte L, Neyt K, Killeen N, Malissen B, Hammad H, Lambrecht BN. 2013. Conventional and monocyte-derived CD11b+ dendritic cells initiate and maintain T helper 2 cell-mediated immunity to house dust mite allergen. Immunity 38:322–335. [PubMed]
137. Soudja SM, Ruiz AL, Marie JC, Lauvau G. 2012. Inflammatory monocytes activate memory CD8+ T and innate NK lymphocytes independent of cognate antigen during microbial pathogen invasion. Immunity 37:549–562. [PubMed]
138. Rotta G, Edwards EW, Sangaletti S, Bennett C, Ronzoni S, Colombo MP, Steinman RM, Randolph GJ, Rescigno M. 2003. Lipopolysaccharide or whole bacteria block the conversion of inflammatory monocytes into dendritic cells in vivo. J Exp Med 198:1253–1263. [PubMed]
139. Randolph GJ, Beaulieu S, Lebecque S, Steinman RM, Muller WA. 1998. Differentiation of monocytes into dendritic cells in a model of transendothelial trafficking. Science 282:480–483. [PubMed]
140. Randolph GJ, Sanchez-Schmitz G, Liebman RM, Schäkel K. 2002. The CD16+ (FcγRIII+) subset of human monocytes preferentially becomes migratory dendritic cells in a model tissue setting. J Exp Med 196:517–527. [PubMed]
141. Randolph GJ, Inaba K, Robbiani DF, Steinman RM, Muller WA. 1999. Differentiation of phagocytic monocytes into lymph node dendritic cells in vivo. Immunity 11:753–761. [PubMed]
142. Kudo S, Matsuno K, Ezaki T, Ogawa M. 1997. A novel migration pathway for rat dendritic cells from the blood: hepatic sinusoids-lymph translocation. J Exp Med 185:777–784. [PubMed]
143. Matsuno K, Ezaki T, Kudo S, Uehara Y. 1996. A life stage of particle-laden rat dendritic cells in vivo: their terminal division, active phagocytosis, and translocation from the liver to the draining lymph. J Exp Med 183:1865–1878. [PubMed]
144. Yu B, Ueta H, Kitazawa Y, Tanaka T, Adachi K, Kimura H, Morita M, Sawanobori Y, Qian HX, Kodama T, Matsuno K. 2012. Two immunogenic passenger dendritic cell subsets in the rat liver have distinct trafficking patterns and radiosensitivities. Hepatology 56:1532–1545. [PubMed]
145. Qu C, Brinck-Jensen N-S, Zang M, Chen K. 2014. Monocyte-derived dendritic cells: targets as potent antigen-presenting cells for the design of vaccines against infectious diseases. Int J Infect Dis 19:1–5. [PubMed]
146. de Jong A, Cheng TY, Huang S, Gras S, Birkinshaw RW, Kasmar AG, Van Rhijn I, Peña-Cruz V, Ruan DT, Altman JD, Rossjohn J, Moody DB. 2014. CD1a-autoreactive T cells recognize natural skin oils that function as headless antigens. Nat Immunol 15:177–185. [PubMed]
147. Kubo A, Nagao K, Yokouchi M, Sasaki H, Amagai M. 2009. External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers. J Exp Med 206:2937–2946. [PubMed]
148. Flacher V, Tripp CH, Mairhofer DG, Steinman RM, Stoitzner P, Idoyaga J, Romani N. 2014. Murine Langerin+ dermal dendritic cells prime CD8+ T cells while Langerhans cells induce cross-tolerance. EMBO Mol Med 6:1191–1204. [PubMed]
149. Seneschal J, Clark RA, Gehad A, Baecher-Allan CM, Kupper TS. 2012. Human epidermal Langerhans cells maintain immune homeostasis in skin by activating skin resident regulatory T cells. Immunity 36:873–884. [PubMed]
150. Kim M, Truong NR, James V, Bosnjak L, Sandgren KJ, Harman AN, Nasr N, Bertram KM, Olbourne N, Sawleshwarkar S, McKinnon K, Cohen RC, Cunningham AL. 2015. Relay of herpes simplex virus between Langerhans cells and dermal dendritic cells in human skin. PLoS Pathog 11:e1004812. doi:10.1371/journal.ppat.1004812.
151. Hoeffel G, Wang Y, Greter M, See P, Teo P, Malleret B, Leboeuf M, Low D, Oller G, Almeida F, Choy SHY, Grisotto M, Renia L, Conway SJ, Stanley ER, Chan JKY, Ng LG, Samokhvalov IM, Merad M, Ginhoux F. 2012. Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. J Exp Med 209:1167–1181. [PubMed]
152. Schuster C, Mildner M, Mairhofer M, Bauer W, Fiala C, Prior M, Eppel W, Kolbus A, Tschachler E, Stingl G, Elbe-Bürger A. 2014. Human embryonic epidermis contains a diverse Langerhans cell precursor pool. Development 141:807–815. [PubMed]
153. Ginhoux F, Jung S. 2014. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol 14:392–404. [PubMed]
154. Sheng J, Ruedl C, Karjalainen K. 2015. Most tissue-resident macrophages except microglia are derived from fetal hematopoietic stem cells. Immunity 43:382–393. [PubMed]
155. Capucha T, Mizraji G, Segev H, Blecher-Gonen R, Winter D, Khalaileh A, Tabib Y, Attal T, Nassar M, Zelentsova K, Kisos H, Zenke M, Seré K, Hieronymus T, Burstyn-Cohen T, Amit I, Wilensky A, Hovav AH. 2015. Distinct murine mucosal Langerhans cell subsets develop from pre-dendritic cells and monocytes. Immunity 43:369–381. [PubMed]
156. Liu C, Duffy B, Bednarski JJ, Calhoun C, Lay L, Rundblad B, Payton JE, Mohanakumar T. 2016. Maternal T-cell engraftment interferes with human leukocyte antigen typing in severe combined immunodeficiency. Am J Clin Pathol 145:251–257. [PubMed]
157. Buckley RH, Schiff RI, Schiff SE, Markert ML, Williams LW, Harville TO, Roberts JL, Puck JM. 1997. Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. J Pediatr 130:378–387.
158. Dawe GS, Tan XW, Xiao ZC. 2007. Cell migration from baby to mother. Cell Adhes Migr 1:19–27. [PubMed]
159. Nijagal A, Wegorzewska M, Jarvis E, Le T, Tang Q, MacKenzie TC. 2011. Maternal T cells limit engraftment after in utero hematopoietic cell transplantation in mice. J Clin Invest 121:582–592. [PubMed]
160. Malissen B, Tamoutounour S, Henri S. 2014. The origins and functions of dendritic cells and macrophages in the skin. Nat Rev Immunol 14:417–428. [PubMed]
161. Beijer MR, Molenaar R, Goverse G, Mebius RE, Kraal G, den Haan JM. 2013. A crucial role for retinoic acid in the development of Notch-dependent murine splenic CD8CD4 and CD4+ dendritic cells. Eur J Immunol 43:1608–1616. [PubMed]
162. Iwasaki A, Kelsall BL. 2001. Unique functions of CD11b+, CD8α+, and double-negative Peyer’s patch dendritic cells. J Immunol 166:4884–4890. [PubMed]
163. De Jesus M, Ostroff GR, Levitz SM, Bartling TR, Mantis NJ. 2014. A population of Langerin-positive dendritic cells in murine Peyer’s patches involved in sampling β-glucan microparticles. PLoS One 9:e91002. doi:10.1371/journal.pone.0091002.
164. Cerovic V, Bain CC, Mowat AM, Milling SW. 2014. Intestinal macrophages and dendritic cells: what’s the difference? Trends Immunol 35:270–277. [PubMed]
165. Belkaid Y, Segre JA. 2014. Dialogue between skin microbiota and immunity. Science 346:954–959. [PubMed]
166. Belkaid Y, Naik S. 2013. Compartmentalized and systemic control of tissue immunity by commensals. Nat Immunol 14:646–653. [PubMed]
167. Belkaid Y, Bouladoux N, Hand TW. 2013. Effector and memory T cell responses to commensal bacteria. Trends Immunol 34:299–306. [PubMed]
168. Bessman NJ, Sonnenberg GF. 2016. Emerging roles for antigen presentation in establishing host-microbiome symbiosis. Immunol Rev 272:139–150. [PubMed]
169. Cullender TC, Chassaing B, Janzon A, Kumar K, Muller CE, Werner JJ, Angenent LT, Bell ME, Hay AG, Peterson DA, Walter J, Vijay-Kumar M, Gewirtz AT, Ley RE. 2013. Innate and adaptive immunity interact to quench microbiome flagellar motility in the gut. Cell Host Microbe 14:571–581. [PubMed]
170. Miyake K, Kaisho T. 2014. Homeostatic inflammation in innate immunity. Curr Opin Immunol 30:85–90. [PubMed]
171. Heath WR, Carbone FR. 2013. The skin-resident and migratory immune system in steady state and memory: innate lymphocytes, dendritic cells and T cells. Nat Immunol 14:978–985. [PubMed]
172. Nestle FO, Di Meglio P, Qin JZ, Nickoloff BJ. 2009. Skin immune sentinels in health and disease. Nat Rev Immunol 9:679–691. [PubMed]
173. Naik S, Bouladoux N, Linehan JL, Han SJ, Harrison OJ, Wilhelm C, Conlan S, Himmelfarb S, Byrd AL, Deming C, Quinones M, Brenchley JM, Kong HH, Tussiwand R, Murphy KM, Merad M, Segre JA, Belkaid Y. 2015. Commensal-dendritic-cell interaction specifies a unique protective skin immune signature. Nature 520:104–108. [PubMed]
174. Shklovskaya E, O’Sullivan BJ, Ng LG, Roediger B, Thomas R, Weninger W, Fazekas de St Groth B. 2011. Langerhans cells are precommitted to immune tolerance induction. Proc Natl Acad Sci U S A 108:18049–18054. [PubMed]
175. Modi BG, Neustadter J, Binda E, Lewis J, Filler RB, Roberts SJ, Kwong BY, Reddy S, Overton JD, Galan A, Tigelaar R, Cai L, Fu P, Shlomchik M, Kaplan DH, Hayday A, Girardi M. 2012. Langerhans cells facilitate epithelial DNA damage and squamous cell carcinoma. Science 335:104–108. [PubMed]
176. Ouchi T, Kubo A, Yokouchi M, Adachi T, Kobayashi T, Kitashima DY, Fujii H, Clausen BE, Koyasu S, Amagai M, Nagao K. 2011. Langerhans cell antigen capture through tight junctions confers preemptive immunity in experimental staphylococcal scalded skin syndrome. J Exp Med 208:2607–2613. [PubMed]
177. van der Aar AM, Picavet DI, Muller FJ, de Boer L, van Capel TM, Zaat SA, Bos JD, Janssen H, George TC, Kapsenberg ML, van Ham SM, Teunissen MB, de Jong EC. 2013. Langerhans cells favor skin flora tolerance through limited presentation of bacterial antigens and induction of regulatory T cells. J Invest Dermatol 133:1240–1249. [PubMed]
178. Langlet C, Tamoutounour S, Henri S, Luche H, Ardouin L, Grégoire C, Malissen B, Guilliams M. 2012. CD64 expression distinguishes monocyte-derived and conventional dendritic cells and reveals their distinct role during intramuscular immunization. J Immunol 188:1751–1760. [PubMed]
179. Kissenpfennig A, Henri S, Dubois B, Laplace-Builhé C, Perrin P, Romani N, Tripp CH, Douillard P, Leserman L, Kaiserlian D, Saeland S, Davoust J, Malissen B. 2005. Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. Immunity 22:643–654. [PubMed]
180. Moussion C, Girard JP. 2011. Dendritic cells control lymphocyte entry to lymph nodes through high endothelial venules. Nature 479:542–546. [PubMed]
181. Palframan RT, Jung S, Cheng G, Weninger W, Luo Y, Dorf M, Littman DR, Rollins BJ, Zweerink H, Rot A, von Andrian UH. 2001. Inflammatory chemokine transport and presentation in HEV: a remote control mechanism for monocyte recruitment to lymph nodes in inflamed tissues. J Exp Med 194:1361–1373. [PubMed]
182. Mueller SN, Germain RN. 2009. Stromal cell contributions to the homeostasis and functionality of the immune system. Nat Rev Immunol 9:618–629. [PubMed]
183. Qi H, Kastenmüller W, Germain RN. 2014. Spatiotemporal basis of innate and adaptive immunity in secondary lymphoid tissue. Annu Rev Cell Dev Biol 30:141–167. [PubMed]
184. Malhotra D, Fletcher AL, Turley SJ. 2013. Stromal and hematopoietic cells in secondary lymphoid organs: partners in immunity. Immunol Rev 251:160–176. [PubMed]
185. Rantakari P, Auvinen K, Jäppinen N, Kapraali M, Valtonen J, Karikoski M, Gerke H, Iftakhar-E-Khuda I, Keuschnigg J, Umemoto E, Tohya K, Miyasaka M, Elima K, Jalkanen S, Salmi M. 2015. The endothelial protein PLVAP in lymphatics controls the entry of lymphocytes and antigens into lymph nodes. Nat Immunol 16:386–396. [PubMed]
186. Gretz JE, Norbury CC, Anderson AO, Proudfoot AE, Shaw S. 2000. Lymph-borne chemokines and other low molecular weight molecules reach high endothelial venules via specialized conduits while a functional barrier limits access to the lymphocyte microenvironments in lymph node cortex. J Exp Med 192:1425–1440. [PubMed]
187. Roozendaal R, Mempel TR, Pitcher LA, Gonzalez SF, Verschoor A, Mebius RE, von Andrian UH, Carroll MC. 2009. Conduits mediate transport of low-molecular-weight antigen to lymph node follicles. Immunity 30:264–276. [PubMed]
188. Acton SE, Reis e Sousa C. 2016. Dendritic cells in remodeling of lymph nodes during immune responses. Immunol Rev 271:221–229. [PubMed]
189. Acton SE, Farrugia AJ, Astarita JL, Mourão-Sá D, Jenkins RP, Nye E, Hooper S, van Blijswijk J, Rogers NC, Snelgrove KJ, Rosewell I, Moita LF, Stamp G, Turley SJ, Sahai E, Reis e Sousa C. 2014. Dendritic cells control fibroblastic reticular network tension and lymph node expansion. Nature 514:498–502. [PubMed]
190. Sixt M, Kanazawa N, Selg M, Samson T, Roos G, Reinhardt DP, Pabst R, Lutz MB, Sorokin L. 2005. The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node. Immunity 22:19–29. [PubMed]
191. Jakubzick C, Bogunovic M, Bonito AJ, Kuan EL, Merad M, Randolph GJ. 2008. Lymph-migrating, tissue-derived dendritic cells are minor constituents within steady-state lymph nodes. J Exp Med 205:2839–2850. [PubMed]
192. Gerner MY, Kastenmuller W, Ifrim I, Kabat J, Germain RN. 2012. Histo-cytometry: a method for highly multiplex quantitative tissue imaging analysis applied to dendritic cell subset microanatomy in lymph nodes. Immunity 37:364–376. [PubMed]
193. Gerner MY, Torabi-Parizi P, Germain RN. 2015. Strategically localized dendritic cells promote rapid T cell responses to lymph-borne particulate antigens. Immunity 42:172–185. [PubMed]
194. Guilliams M, Crozat K, Henri S, Tamoutounour S, Grenot P, Devilard E, de Bovis B, Alexopoulou L, Dalod M, Malissen B. 2010. Skin-draining lymph nodes contain dermis-derived CD103 dendritic cells that constitutively produce retinoic acid and induce Foxp3+ regulatory T cells. Blood 115:1958–1968. [PubMed]
195. Catron DM, Itano AA, Pape KA, Mueller DL, Jenkins MK. 2004. Visualizing the first 50 hr of the primary immune response to a soluble antigen. Immunity 21:341–347. [PubMed]
196. Itano AA, McSorley SJ, Reinhardt RL, Ehst BD, Ingulli E, Rudensky AY, Jenkins MK. 2003. Distinct dendritic cell populations sequentially present antigen to CD4 T cells and stimulate different aspects of cell-mediated immunity. Immunity 19:47–57.
197. Thurley K, Gerecht D, Friedmann E, Höfer T. 2015. Three-dimensional gradients of cytokine signaling between T cells. PLoS Comput Biol 11:e1004206. doi:10.1371/journal.pcbi.1004206. [PubMed]
198. Hor JL, Whitney PG, Zaid A, Brooks AG, Heath WR, Mueller SN. 2015. Spatiotemporally distinct interactions with dendritic cell subsets facilitates CD4+ and CD8+ T cell activation to localized viral infection. Immunity 43:554–565. [PubMed]
199. Eickhoff S, Brewitz A, Gerner MY, Klauschen F, Komander K, Hemmi H, Garbi N, Kaisho T, Germain RN, Kastenmüller W. 2015. Robust anti-viral immunity requires multiple distinct T cell-dendritic cell interactions. Cell 162:1322–1337. [PubMed]
200. Smith CM, Wilson NS, Waithman J, Villadangos JA, Carbone FR, Heath WR, Belz GT. 2004. Cognate CD4+ T cell licensing of dendritic cells in CD8+ T cell immunity. Nat Immunol 5:1143–1148. [PubMed]
201. Zaccard CR, Watkins SC, Kalinski P, Fecek RJ, Yates AL, Salter RD, Ayyavoo V, Rinaldo CR, Mailliard RB. 2015. CD40L induces functional tunneling nanotube networks exclusively in dendritic cells programmed by mediators of type 1 immunity. J Immunol 194:1047–1056. [PubMed]
202. Junt T, Scandella E, Ludewig B. 2008. Form follows function: lymphoid tissue microarchitecture in antimicrobial immune defence. Nat Rev Immunol 8:764–775. [PubMed]
203. Bernhard CA, Ried C, Kochanek S, Brocker T. 2015. CD169+ macrophages are sufficient for priming of CTLs with specificities left out by cross-priming dendritic cells. Proc Natl Acad Sci U S A 112:5461–5466. [PubMed]
204. Bain CC, Mowat AM. 2014. Macrophages in intestinal homeostasis and inflammation. Immunol Rev 260:102–117. [PubMed]
205. Jung C, Hugot J-P, Barreau F. 2010. Peyer’s patches: the immune sensors of the intestine. Int J Inflamm 2010:823710. [PubMed]
206. Kruglov AA, Grivennikov SI, Kuprash DV, Winsauer C, Prepens S, Seleznik GM, Eberl G, Littman DR, Heikenwalder M, Tumanov AV, Nedospasov SA. 2013. Nonredundant function of soluble LTα3 produced by innate lymphoid cells in intestinal homeostasis. Science 342:1243–1246. [PubMed]
207. Mowat AM, Agace WW. 2014. Regional specialization within the intestinal immune system. Nat Rev Immunol 14:667–685. [PubMed]
208. Pugh CW, MacPherson GG, Steer HW. 1983. Characterization of nonlymphoid cells derived from rat peripheral lymph. J Exp Med 157:1758–1779. [PubMed]
209. Bain CC, Scott CL, Uronen-Hansson H, Gudjonsson S, Jansson O, Grip O, Guilliams M, Malissen B, Agace WW, Mowat AM. 2013. Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6Chi monocyte precursors. Mucosal Immunol 6:498–510. [PubMed]
210. Mazzini E, Massimiliano L, Penna G, Rescigno M. 2014. Oral tolerance can be established via gap junction transfer of fed antigens from CX3CR1+ macrophages to CD103+ dendritic cells. Immunity 40:248–261. [PubMed]
211. Scott CL, Bain CC, Wright PB, Sichien D, Kotarsky K, Persson EK, Luda K, Guilliams M, Lambrecht BN, Agace WW, Milling SW, Mowat AM. 2015. CCR2+CD103 intestinal dendritic cells develop from DC-committed precursors and induce interleukin-17 production by T cells. Mucosal Immunol 8:327–339. [PubMed]
212. Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, Bonasio R, Granucci F, Kraehenbuhl JP, Ricciardi-Castagnoli P. 2001. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2:361–367. [PubMed]
213. Chieppa M, Rescigno M, Huang AYC, Germain RN. 2006. Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. J Exp Med 203:2841–2852. [PubMed]
214. McDole JR, Wheeler LW, McDonald KG, Wang B, Konjufca V, Knoop KA, Newberry RD, Miller MJ. 2012. Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine. Nature 483:345–349. [PubMed]
215. Shakhar G, Kolesnikov M. 2014. Intestinal macrophages and DCs close the gap on tolerance. Immunity 40:171–173. [PubMed]
216. Diehl GE, Longman RS, Zhang J-X, Breart B, Galan C, Cuesta A, Schwab SR, Littman DR. 2013. Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX3CR1hi cells. Nature 494:116–120. [PubMed]
217. Farache J, Koren I, Milo I, Gurevich I, Kim K-W, Zigmond E, Furtado GC, Lira SA, Shakhar G. 2013. Luminal bacteria recruit CD103+ dendritic cells into the intestinal epithelium to sample bacterial antigens for presentation. Immunity 38:581–595. [PubMed]
218. Coombes JL, Siddiqui KRR, Arancibia-Cárcamo CV, Hall J, Sun CM, Belkaid Y, Powrie F. 2007. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-β and retinoic acid-dependent mechanism. J Exp Med 204:1757–1764. [PubMed]
219. Coombes JL, Powrie F. 2008. Dendritic cells in intestinal immune regulation. Nat Rev Immunol 8:435–446. [PubMed]
220. Travis MA, Reizis B, Melton AC, Masteller E, Tang Q, Proctor JM, Wang Y, Bernstein X, Huang X, Reichardt LF, Bluestone JA, Sheppard D. 2007. Loss of integrin αvβ8 on dendritic cells causes autoimmunity and colitis in mice. Nature 449:361–365. [PubMed]
221. Muzaki ARBM, Tetlak P, Sheng J, Loh SC, Setiagani YA, Poidinger M, Zolezzi F, Karjalainen K, Ruedl C. 2016. Intestinal CD103+CD11b dendritic cells restrain colitis via IFN-γ-induced anti-inflammatory response in epithelial cells. Mucosal Immunol 9:336–351. [PubMed]
222. van de Pavert SA, Mebius RE. 2010. New insights into the development of lymphoid tissues. Nat Rev Immunol 10:664–674. [PubMed]
223. Tanoue T, Atarashi K, Honda K. 2016. Development and maintenance of intestinal regulatory T cells. Nat Rev Immunol 16:295–309. [PubMed]
224. Worbs T, Bode U, Yan S, Hoffmann MW, Hintzen G, Bernhardt G, Förster R, Pabst O. 2006. Oral tolerance originates in the intestinal immune system and relies on antigen carriage by dendritic cells. J Exp Med 203:519–527. [PubMed]
225. Macpherson AJ, Smith K. 2006. Mesenteric lymph nodes at the center of immune anatomy. J Exp Med 203:497–500. [PubMed]
226. Balmer ML, Slack E, de Gottardi A, Lawson MAE, Hapfelmeier S, Miele L, Grieco A, Van Vlierberghe H, Fahrner R, Patuto N, Bernsmeier C, Ronchi F, Wyss M, Stroka D, Dickgreber N, Heim MH, McCoy KD, Macpherson AJ. 2014. The liver may act as a firewall mediating mutualism between the host and its gut commensal microbiota. Sci Transl Med 6:237ra66. doi:10.1126/scitranslmed.3008618.
227. Yrlid U, Cerovic V, Milling S, Jenkins CD, Zhang J, Crocker PR, Klavinskis LS, MacPherson GG. 2006. Plasmacytoid dendritic cells do not migrate in intestinal or hepatic lymph. J Immunol 177:6115–6121. [PubMed]
228. Yang JY, Kim MS, Kim E, Cheon JH, Lee YS, Kim Y, Lee SH, Seo SU, Shin SH, Choi SS, Kim B, Chang SY, Ko HJ, Bae JW, Kweon MN. 2016. Enteric viruses ameliorate gut inflammation via Toll-like receptor 3 and Toll-like receptor 7-mediated interferon-β production. Immunity 44:889–900. [PubMed]
229. Reboldi A, Cyster JG. 2016. Peyer’s patches: organizing B-cell responses at the intestinal frontier. Immunol Rev 271:230–245. [PubMed]
230. Bonnardel J, Da Silva C, Henri S, Tamoutounour S, Chasson L, Montañana-Sanchis F, Gorvel J-P, Lelouard H. 2015. Innate and adaptive immune functions of Peyer’s patch monocyte-derived cells. Cell Rep 11:770–784. [PubMed]
231. Bonnardel J, Da Silva C, Masse M, Montañana-Sanchis F, Gorvel JP, Lelouard H. 2015. Gene expression profiling of the Peyer’s patch mononuclear phagocyte system. Genom Data 5:21–24. [PubMed]
232. Lelouard H, Fallet M, de Bovis B, Méresse S, Gorvel J-P. 2012. Peyer’s patch dendritic cells sample antigens by extending dendrites through M cell-specific transcellular pores. Gastroenterology 142:592–601.e3. doi:10.1053/j.gastro.2011.11.039.
233. Macpherson AJ, McCoy KD. 2015. Independence Day for IgA. Immunity 43:416–418. [PubMed]
234. Cook PC, MacDonald AS. 2016. Dendritic cells in lung immunopathology. Semin Immunopathol 38:449–460. [PubMed]
235. Kopf M, Schneider C, Nobs SP. 2015. The development and function of lung-resident macrophages and dendritic cells. Nat Immunol 16:36–44. [PubMed]
236. Sung S-SJ, Fu SM, Rose CE Jr, Gaskin F, Ju S-T, Beaty SR. 2006. A major lung CD103 (αE)-β7 integrin-positive epithelial dendritic cell population expressing Langerin and tight junction proteins. J Immunol 176:2161–2172. [PubMed]
237. Thornton EE, Looney MR, Bose O, Sen D, Sheppard D, Locksley R, Huang X, Krummel MF. 2012. Spatiotemporally separated antigen uptake by alveolar dendritic cells and airway presentation to T cells in the lung. J Exp Med 209:1183–1199. [PubMed]
238. Bonduelle O, Duffy D, Verrier B, Combadière C, Combadière B. 2012. Cutting edge: protective effect of CX3CR1+ dendritic cells in a vaccinia virus pulmonary infection model. J Immunol 188:952–956. [PubMed]
239. Desch AN, Randolph GJ, Murphy K, Gautier EL, Kedl RM, Lahoud MH, Caminschi I, Shortman K, Henson PM, Jakubzick CV. 2011. CD103+ pulmonary dendritic cells preferentially acquire and present apoptotic cell-associated antigen. J Exp Med 208:1789–1797. [PubMed]
240. Takano K, Kojima T, Go M, Murata M, Ichimiya S, Himi T, Sawada N. 2005. HLA-DR- and CD11c-positive dendritic cells penetrate beyond well-developed epithelial tight junctions in human nasal mucosa of allergic rhinitis. J Histochem Cytochem 53:611–619. [PubMed]
241. Helft J, Manicassamy B, Guermonprez P, Hashimoto D, Silvin A, Agudo J, Brown BD, Schmolke M, Miller JC, Leboeuf M, Murphy KM, García-Sastre A, Merad M. 2012. Cross-presenting CD103+ dendritic cells are protected from influenza virus infection. J Clin Invest 122:4037–4047. [PubMed]
242. Abraham SN, Miao Y. 2015. The nature of immune responses to urinary tract infections. Nat Rev Immunol 15:655–663. [PubMed]
243. Dieterlen MT, John K, Reichenspurner H, Mohr FW, Barten MJ. 2016. Dendritic cells and their role in cardiovascular diseases: a view on human studies. J Immunol Res 2016:5946807. doi:10.1155/2016/5946807. [PubMed]
244. Busch M, Westhofen TC, Koch M, Lutz MB, Zernecke A. 2014. Dendritic cell subset distributions in the aorta in healthy and atherosclerotic mice. PLoS One 9:e88452. doi:10.1371/journal.pone.0088452. [PubMed]
245. Choi JH, Do Y, Cheong C, Koh H, Boscardin SB, Oh YS, Bozzacco L, Trumpfheller C, Park CG, Steinman RM. 2009. Identification of antigen-presenting dendritic cells in mouse aorta and cardiac valves. J Exp Med 206:497–505. [PubMed]
246. Rogers NM, Ferenbach DA, Isenberg JS, Thomson AW, Hughes J. 2014. Dendritic cells and macrophages in the kidney: a spectrum of good and evil. Nat Rev Nephrol 10:625–643. [PubMed]
247. Gottschalk C, Kurts C. 2015. The debate about dendritic cells and macrophages in the kidney. Front Immunol 6:435. doi:10.3389/fimmu.2015.00435. [PubMed]
248. Ferris ST, Carrero JA, Mohan JF, Calderon B, Murphy KM, Unanue ER. 2014. A minor subset of Batf3-dependent antigen-presenting cells in islets of Langerhans is essential for the development of autoimmune diabetes. Immunity 41:657–669. [PubMed]
249. Epelman S, Lavine KJ, Beaudin AE, Sojka DK, Carrero JA, Calderon B, Brija T, Gautier EL, Ivanov S, Satpathy AT, Schilling JD, Schwendener R, Sergin I, Razani B, Forsberg EC, Yokoyama WM, Unanue ER, Colonna M, Randolph GJ, Mann DL. 2014. Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation. Immunity 40:91–104. [PubMed]
250. Larsen CP, Morris PJ, Austyn JM. 1990. Donor dendritic leukocytes migrate from cardiac allografts into recipients’ spleens. Transplant Proc 22:1943–1944. [PubMed]
251. Aspelund A, Robciuc MR, Karaman S, Makinen T, Alitalo K. 2016. Lymphatic system in cardiovascular medicine. Circ Res 118:515–530. [PubMed]
252. Cavanagh LL, Bonasio R, Mazo IB, Halin C, Cheng G, van der Velden AW, Cariappa A, Chase C, Russell P, Starnbach MN, Koni PA, Pillai S, Weninger W, von Andrian UH. 2005. Activation of bone marrow-resident memory T cells by circulating, antigen-bearing dendritic cells. Nat Immunol 6:1029–1037. [PubMed]
253. Hervouet C, Luci C, Bekri S, Juhel T, Bihl F, Braud VM, Czerkinsky C, Anjuère F. 2014. Antigen-bearing dendritic cells from the sublingual mucosa recirculate to distant systemic lymphoid organs to prime mucosal CD8 T cells. Mucosal Immunol 7:280–291. [PubMed]
254. Steiniger BS. 2015. Human spleen microanatomy: why mice do not suffice. Immunology 145:334–346. [PubMed]
255. Yi T, Cyster JG. 2013. EBI2-mediated bridging channel positioning supports splenic dendritic cell homeostasis and particulate antigen capture. eLife 2:e00757. doi:10.7554/eLife.00757. [PubMed]
256. Gatto D, Wood K, Caminschi I, Murphy-Durland D, Schofield P, Christ D, Karupiah G, Brink R. 2013. The chemotactic receptor EBI2 regulates the homeostasis, localization and immunological function of splenic dendritic cells. Nat Immunol 14:446–453. [PubMed]
257. Yi T, Li J, Chen H, Wu J, An J, Xu Y, Hu Y, Lowell CA, Cyster JG. 2015. Splenic dendritic cells survey red blood cells for missing self-CD47 to trigger adaptive immune responses. Immunity 43:764–775. [PubMed]
258. Qiu CH, Miyake Y, Kaise H, Kitamura H, Ohara O, Tanaka M. 2009. Novel subset of CD8α+ dendritic cells localized in the marginal zone is responsible for tolerance to cell-associated antigens. J Immunol 182:4127–4136. [PubMed]
259. Glennon E, Kaunzner UW, Gagnidze K, McEwen BS, Bulloch K. 2015. Pituitary dendritic cells communicate immune pathogenic signals. Brain Behav Immun 50:232–240. [PubMed]
260. Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, Derecki NC, Castle D, Mandell JW, Lee KS, Harris TH, Kipnis J. 2015. Structural and functional features of central nervous system lymphatic vessels. Nature 523:337–341. [PubMed]
261. Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, Detmar M, Wiig H, Alitalo K. 2015. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med 212:991–999. [PubMed]
262. Chavan SS, Tracey KJ. 2013. Neurophysiologic reflex mechanisms in immunology, p 850–862. In Paul WE (ed), Fundamental Immunology, 7th ed. Lippincott Williams & Wilkins, Philadelphia, PA.
263. Rhee SH, Pothoulakis C, Mayer EA. 2009. Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat Rev Gastroenterol Hepatol 6:306–314. [PubMed]
264. McMahon SB, La Russa F, Bennett DLH. 2015. Crosstalk between the nociceptive and immune systems in host defence and disease. Nat Rev Neurosci 16:389–402. [PubMed]
265. Prado C, Contreras F, González H, Díaz P, Elgueta D, Barrientos M, Herrada AA, Lladser Á, Bernales S, Pacheco R. 2012. Stimulation of dopamine receptor D5 expressed on dendritic cells potentiates Th17-mediated immunity. J Immunol 188:3062–3070. [PubMed]
266. Wülfing C, Günther HS. 2015. Dendritic cells and macrophages neurally hard-wired in the lymph node. Sci Rep 5:16866. doi:10.1038/srep16866. [PubMed]
267. Yarovinsky F. 2014. Innate immunity to Toxoplasma gondii infection. Nat Rev Immunol 14:109–121. [PubMed]
268. Balenga NA, Balenga NA. 2007. Human TLR11 gene is repressed due to its probable interaction with profilin expressed in human. Med Hypotheses 68:456. [PubMed]
269. Abbas AK, Benoist C, Bluestone JA, Campbell DJ, Ghosh S, Hori S, Jiang S, Kuchroo VK, Mathis D, Roncarolo MG, Rudensky A, Sakaguchi S, Shevach EM, Vignali DAA, Ziegler SF. 2013. Regulatory T cells: recommendations to simplify the nomenclature. Nat Immunol 14:307–308. [PubMed]
270. Caramalho Í, Nunes-Cabaço H, Foxall RB, Sousa AE. 2015. Regulatory T-cell development in the human thymus. Front Immunol 6:395. doi:10.3389/fimmu.2015.00395. [PubMed]
271. Panduro M, Benoist C, Mathis D. 2016. Tissue Tregs. Annu Rev Immunol 34:609–633. [PubMed]
272. Li MO, Rudensky AY. 2016. T cell receptor signalling in the control of regulatory T cell differentiation and function. Nat Rev Immunol 16:220–233. [PubMed]
273. Drumea-Mirancea M, Wessels JT, Müller CA, Essl M, Eble JA, Tolosa E, Koch M, Reinhardt DP, Sixt M, Sorokin L, Stierhof YD, Schwarz H, Klein G. 2006. Characterization of a conduit system containing laminin-5 in the human thymus: a potential transport system for small molecules. J Cell Sci 119:1396–1405. [PubMed]
274. Klein L, Kyewski B, Allen PM, Hogquist KA. 2014. Positive and negative selection of the T cell repertoire: what thymocytes see (and don’t see). Nat Rev Immunol 14:377–391. [PubMed]
275. Kurd N, Robey EA. 2016. T-cell selection in the thymus: a spatial and temporal perspective. Immunol Rev 271:114–126. [PubMed]
276. Takaba H, Morishita Y, Tomofuji Y, Danks L, Nitta T, Komatsu N, Kodama T, Takayanagi H. 2015. Fezf2 orchestrates a thymic program of self-antigen expression for immune tolerance. Cell 163:975–987. [PubMed]
277. Gardner JM, Metzger TC, McMahon EJ, Au-Yeung BB, Krawisz AK, Lu W, Price JD, Johannes KP, Satpathy AT, Murphy KM, Tarbell KV, Weiss A, Anderson MS. 2013. Extrathymic Aire-expressing cells are a distinct bone marrow-derived population that induce functional inactivation of CD4+ T cells. Immunity 39:560–572. [PubMed]
278. Lucas B, McCarthy NI, Baik S, Cosway E, James KD, Parnell SM, White AJ, Jenkinson WE, Anderson G. 2016. Control of the thymic medulla and its influence on αβT-cell development. Immunol Rev 271:23–37. [PubMed]
279. Perry JS, Hsieh CS. 2016. Development of T-cell tolerance utilizes both cell-autonomous and cooperative presentation of self-antigen. Immunol Rev 271:141–155. [PubMed]
280. Perry JS, Lio CW, Kau AL, Nutsch K, Yang Z, Gordon JI, Murphy KM, Hsieh CS. 2014. Distinct contributions of Aire and antigen-presenting-cell subsets to the generation of self-tolerance in the thymus. Immunity 41:414–426. [PubMed]
281. Abramson J, Husebye ES. 2016. Autoimmune regulator and self-tolerance—molecular and clinical aspects. Immunol Rev 271:127–140. [PubMed]
282. St-Pierre C, Brochu S, Vanegas JR, Dumont-Lagacé M, Lemieux S, Perreault C. 2013. Transcriptome sequencing of neonatal thymic epithelial cells. Sci Rep 3:1860. doi:10.1038/srep01860. [PubMed]
283. Proietto AI, van Dommelen S, Wu L. 2009. The impact of circulating dendritic cells on the development and differentiation of thymocytes. Immunol Cell Biol 87:39–45. [PubMed]
284. Taniguchi RT, DeVoss JJ, Moon JJ, Sidney J, Sette A, Jenkins MK, Anderson MS. 2012. Detection of an autoreactive T-cell population within the polyclonal repertoire that undergoes distinct autoimmune regulator (Aire)-mediated selection. Proc Natl Acad Sci U S A 109:7847–7852. [PubMed]
285. Yamano T, Nedjic J, Hinterberger M, Steinert M, Koser S, Pinto S, Gerdes N, Lutgens E, Ishimaru N, Busslinger M, Brors B, Kyewski B, Klein L. 2015. Thymic B cells are licensed to present self antigens for central T cell tolerance induction. Immunity 42:1048–1061. [PubMed]
286. Oh J, Shin JS. 2015. The role of dendritic cells in central tolerance. Immune Netw 15:111–120. [PubMed]
287. Osorio F, Fuentes C, López MN, Salazar-Onfray F, González FE. 2015. Role of dendritic cells in the induction of lymphocyte tolerance. Front Immunol 6:535. doi:10.3389/fimmu.2015.00535. [PubMed]
288. Yang S, Fujikado N, Kolodin D, Benoist C, Mathis D. 2015. Immune tolerance. Regulatory T cells generated early in life play a distinct role in maintaining self-tolerance. Science 348:589–594. [PubMed]
289. Hubert FX, Kinkel SA, Davey GM, Phipson B, Mueller SN, Liston A, Proietto AI, Cannon PZ, Forehan S, Smyth GK, Wu L, Goodnow CC, Carbone FR, Scott HS, Heath WR. 2011. Aire regulates the transfer of antigen from mTECs to dendritic cells for induction of thymic tolerance. Blood 118:2462–2472. [PubMed]
290. Proietto AI, van Dommelen S, Zhou P, Rizzitelli A, D’Amico A, Steptoe RJ, Naik SH, Lahoud MH, Liu Y, Zheng P, Shortman K, Wu L. 2008. Dendritic cells in the thymus contribute to T-regulatory cell induction. Proc Natl Acad Sci U S A 105:19869–19874. [PubMed]
291. Bonasio R, Scimone ML, Schaerli P, Grabie N, Lichtman AH, von Andrian UH. 2006. Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus. Nat Immunol 7:1092–1100. [PubMed]
292. Baba T, Nakamoto Y, Mukaida N. 2009. Crucial contribution of thymic Sirpα+ conventional dendritic cells to central tolerance against blood-borne antigens in a CCR2-dependent manner. J Immunol 183:3053–3063. [PubMed]
293. Li J, Park J, Foss D, Goldschneider I. 2009. Thymus-homing peripheral dendritic cells constitute two of the three major subsets of dendritic cells in the steady-state thymus. J Exp Med 206:607–622. [PubMed]
294. Donskoy E, Goldschneider I. 2003. Two developmentally distinct populations of dendritic cells inhabit the adult mouse thymus: demonstration by differential importation of hematogenous precursors under steady state conditions. J Immunol 170:3514–3521. [PubMed]
295. Atibalentja DF, Murphy KM, Unanue ER. 2011. Functional redundancy between thymic CD8α+ and Sirpα+ conventional dendritic cells in presentation of blood-derived lysozyme by MHC class II proteins. J Immunol 186:1421–1431. [PubMed]
296. Hadeiba H, Lahl K, Edalati A, Oderup C, Habtezion A, Pachynski R, Nguyen L, Ghodsi A, Adler S, Butcher EC. 2012. Plasmacytoid dendritic cells transport peripheral antigens to the thymus to promote central tolerance. Immunity 36:438–450. [PubMed]
297. Yadav M, Stephan S, Bluestone JA. 2013. Peripherally induced Tregs—role in immune homeostasis and autoimmunity. Front Immunol 4:232. doi:10.3389/fimmu.2013.00232. [PubMed]
298. Bosco N, Kirberg J, Ceredig R, Agenès F. 2009. Peripheral T cells in the thymus: have they just lost their way or do they do something? Immunol Cell Biol 87:50–57. [PubMed]
299. Josefowicz SZ, Lu LF, Rudensky AY. 2012. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol 30:531–564. [PubMed]
300. Leventhal DS, Gilmore DC, Berger JM, Nishi S, Lee V, Malchow S, Kline DE, Kline J, Vander Griend DJ, Huang H, Socci ND, Savage PA. 2016. Dendritic cells coordinate the development and homeostasis of organ-specific regulatory T cells. Immunity 44:847–859. [PubMed]
301. Scharschmidt TC, Vasquez KS, Truong HA, Gearty SV, Pauli ML, Nosbaum A, Gratz IK, Otto M, Moon JJ, Liese J, Abbas AK, Fischbach MA, Rosenblum MD. 2015. A wave of regulatory T cells into neonatal skin mediates tolerance to commensal microbes. Immunity 43:1011–1021. [PubMed]
302. Legoux FP, Lim J-B, Cauley AW, Dikiy S, Ertelt J, Mariani TJ, Sparwasser T, Way SS, Moon JJ. 2015. CD4+ T cell tolerance to tissue-restricted self antigens is mediated by antigen-specific regulatory T cells rather than deletion. Immunity 43:896–908. [PubMed]
303. Kim KS, Hong SW, Han D, Yi J, Jung J, Yang BG, Lee JY, Lee M, Surh CD. 2016. Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine. Science 351:858–863. [PubMed]
304. Rosenblum MD, Way SS, Abbas AK. 2016. Regulatory T cell memory. Nat Rev Immunol 16:90–101. [PubMed]
305. Sanchez Rodriguez R, Pauli ML, Neuhaus IM, Yu SS, Arron ST, Harris HW, Yang SH, Anthony BA, Sverdrup FM, Krow-Lucal E, MacKenzie TC, Johnson DS, Meyer EH, Löhr A, Hsu A, Koo J, Liao W, Gupta R, Debbaneh MG, Butler D, Huynh M, Levin EC, Leon A, Hoffman WY, McGrath MH, Alvarado MD, Ludwig CH, Truong HA, Maurano MM, Gratz IK, Abbas AK, Rosenblum MD. 2014. Memory regulatory T cells reside in human skin. J Clin Invest 124:1027–1036. [PubMed]
306. Eldershaw SA, Sansom DM, Narendran P. 2011. Expression and function of the autoimmune regulator (Aire) gene in non-thymic tissue. Clin Exp Immunol 163:296–308. [PubMed]
307. Lindmark E, Chen Y, Georgoudaki AM, Dudziak D, Lindh E, Adams WC, Loré K, Winqvist O, Chambers BJ, Karlsson MC. 2013. AIRE expressing marginal zone dendritic cells balances adaptive immunity and T-follicular helper cell recruitment. J Autoimmun 42:62–70. [PubMed]
308. Suzuki E, Kobayashi Y, Kawano O, Endo K, Haneda H, Yukiue H, Sasaki H, Yano M, Maeda M, Fujii Y. 2008. Expression of AIRE in thymocytes and peripheral lymphocytes. Autoimmunity 41:133–139. [PubMed]
309. Fletcher AL, Malhotra D, Turley SJ. 2011. Lymph node stroma broaden the peripheral tolerance paradigm. Trends Immunol 32:12–18. [PubMed]
310. Yip L, Su L, Sheng D, Chang P, Atkinson M, Czesak M, Albert PR, Collier AR, Turley SJ, Fathman CG, Creusot RJ. 2009. Deaf1 isoforms control the expression of genes encoding peripheral tissue antigens in the pancreatic lymph nodes during type 1 diabetes. Nat Immunol 10:1026–1033. [PubMed]
311. Dubrot J, Duraes FV, Potin L, Capotosti F, Brighouse D, Suter T, LeibundGut-Landmann S, Garbi N, Reith W, Swartz MA, Hugues S. 2014. Lymph node stromal cells acquire peptide-MHCII complexes from dendritic cells and induce antigen-specific CD4+ T cell tolerance. J Exp Med 211:1153–1166. [PubMed]
312. Campana S, De Pasquale C, Carrega P, Ferlazzo G, Bonaccorsi I. 2015. Cross-dressing: an alternative mechanism for antigen presentation. Immunol Lett 168:349–354. [PubMed]
313. Fletcher AL, Lukacs-Kornek V, Reynoso ED, Pinner SE, Bellemare-Pelletier A, Curry MS, Collier AR, Boyd RL, Turley SJ. 2010. Lymph node fibroblastic reticular cells directly present peripheral tissue antigen under steady-state and inflammatory conditions. J Exp Med 207:689–697. [PubMed]
314. Scheinecker C, McHugh R, Shevach EM, Germain RN. 2002. Constitutive presentation of a natural tissue autoantigen exclusively by dendritic cells in the draining lymph node. J Exp Med 196:1079–1090. [PubMed]
315. Liu Z, Gerner MY, Van Panhuys N, Levine AG, Rudensky AY, Germain RN. 2015. Immune homeostasis enforced by co-localized effector and regulatory T cells. Nature 528:225–230. [PubMed]
316. Loschko J, Schreiber HA, Rieke GJ, Esterházy D, Meredith MM, Pedicord VA, Yao KH, Caballero S, Pamer EG, Mucida D, Nussenzweig MC. 2016. Absence of MHC class II on cDCs results in microbial-dependent intestinal inflammation. J Exp Med 213:517–534. [PubMed]
317. Muth S, Schütze K, Schild H, Probst HC. 2012. Release of dendritic cells from cognate CD4+ T-cell recognition results in impaired peripheral tolerance and fatal cytotoxic T-cell mediated autoimmunity. Proc Natl Acad Sci U S A 109:9059–9064. [PubMed]
318. Schildknecht A, Brauer S, Brenner C, Lahl K, Schild H, Sparwasser T, Probst HC, van den Broek M. 2010. FoxP3+ regulatory T cells essentially contribute to peripheral CD8+ T-cell tolerance induced by steady-state dendritic cells. Proc Natl Acad Sci U S A 107:199–203. [PubMed]
319. Probst HC, McCoy K, Okazaki T, Honjo T, van den Broek M. 2005. Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4. Nat Immunol 6:280–286. [PubMed]
320. Shimoda M, Mmanywa F, Joshi SK, Li T, Miyake K, Pihkala J, Abbas JA, Koni PA. 2006. Conditional ablation of MHC-II suggests an indirect role for MHC-II in regulatory CD4 T cell maintenance. J Immunol 176:6503–6511. [PubMed]
321. Baratin M, Foray C, Demaria O, Habbeddine M, Pollet E, Maurizio J, Verthuy C, Davanture S, Azukizawa H, Flores-Langarica A, Dalod M, Lawrence T. 2015. Homeostatic NF-κB signaling in steady-state migratory dendritic cells regulates immune homeostasis and tolerance. Immunity 42:627–639. [PubMed]
322. Suffner J, Hochweller K, Kühnle MC, Li X, Kroczek RA, Garbi N, Hämmerling GJ. 2010. Dendritic cells support homeostatic expansion of Foxp3+ regulatory T cells in Foxp3. LuciDTR mice. J Immunol 184:1810–1820. [PubMed]
323. Lubkov V, Bar-Sagi D. 2014. E-cadherin-mediated cell coupling is required for apoptotic cell extrusion. Curr Biol 24:868–874. [PubMed]
324. Jiang A, Bloom O, Ono S, Cui W, Unternaehrer J, Jiang S, Whitney JA, Connolly J, Banchereau J, Mellman I. 2007. Disruption of E-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cell maturation. Immunity 27:610–624. [PubMed]
325. Ohnmacht C, Pullner A, King SBS, Drexler I, Meier S, Brocker T, Voehringer D. 2009. Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity. J Exp Med 206:549–559. [PubMed]
326. Birnberg T, Bar-On L, Sapoznikov A, Caton ML, Cervantes-Barragán L, Makia D, Krauthgamer R, Brenner O, Ludewig B, Brockschnieder D, Riethmacher D, Reizis B, Jung S. 2008. Lack of conventional dendritic cells is compatible with normal development and T cell homeostasis, but causes myeloid proliferative syndrome. Immunity 29:986–997. [PubMed]
327. Eberl G, Colonna M, Di Santo JP, McKenzie ANJ. 2015. Innate lymphoid cells: a new paradigm in immunology. Science 348:aaa6566. doi:10.1126/science.aaa6566. [PubMed]
328. McKenzie AN, Spits H, Eberl G. 2014. Innate lymphoid cells in inflammation and immunity. Immunity 41:366–374. [PubMed]
329. Hazenberg MD, Spits H. 2014. Human innate lymphoid cells. Blood 124:700–709. [PubMed]
330. Bar-Ephraïm YE, Mebius RE. 2016. Innate lymphoid cells in secondary lymphoid organs. Immunol Rev 271:185–199. [PubMed]
331. Manh TP, Alexandre Y, Baranek T, Crozat K, Dalod M. 2013. Plasmacytoid, conventional, and monocyte-derived dendritic cells undergo a profound and convergent genetic reprogramming during their maturation. Eur J Immunol 43:1706–1715. [PubMed]
332. Shalek AK, Satija R, Adiconis X, Gertner RS, Gaublomme JT, Raychowdhury R, Schwartz S, Yosef N, Malboeuf C, Lu D, Trombetta JJ, Gennert D, Gnirke A, Goren A, Hacohen N, Levin JZ, Park H, Regev A. 2013. Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells. Nature 498:236–240. [PubMed]
333. Shalek AK, Satija R, Shuga J, Trombetta JJ, Gennert D, Lu D, Chen P, Gertner RS, Gaublomme JT, Yosef N, Schwartz S, Fowler B, Weaver S, Wang J, Wang X, Ding R, Raychowdhury R, Friedman N, Hacohen N, Park H, May AP, Regev A. 2014. Single-cell RNA-seq reveals dynamic paracrine control of cellular variation. Nature 510:363–369.
334. DuPage M, Bluestone JA. 2016. Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease. Nat Rev Immunol 16:149–163. [PubMed]
335. Mori L, Lepore M, De Libero G. 2016. The immunology of CD1- and MR1-restricted T cells. Annu Rev Immunol 34:479–510. [PubMed]
336. Wang D, Sun B, Feng M, Feng H, Gong W, Liu Q, Ge S. 2015. Role of scavenger receptors in dendritic cell function. Hum Immunol 76:442–446. [PubMed]
337. Vanden Berghe T, Linkermann A, Jouan-Lanhouet S, Walczak H, Vandenabeele P. 2014. Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Nat Rev Mol Cell Biol 15:135–147. [PubMed]
338. Pasparakis M, Vandenabeele P. 2015. Necroptosis and its role in inflammation. Nature 517:311–320. [PubMed]
339. Yang WS, Stockwell BR. 2016. Ferroptosis: death by lipid peroxidation. Trends Cell Biol 26:165–176. [PubMed]
340. Bergsbaken T, Fink SL, Cookson BT. 2009. Pyroptosis: host cell death and inflammation. Nat Rev Microbiol 7:99–109. [PubMed]
341. Kumar V, Dasoveanu DC, Chyou S, Tzeng TC, Rozo C, Liang Y, Stohl W, Fu YX, Ruddle NH, Lu TT. 2015. A dendritic-cell-stromal axis maintains immune responses in lymph nodes. Immunity 42:719–730. [PubMed]
342. Roozendaal R, Mebius RE. 2011. Stromal cell-immune cell interactions. Annu Rev Immunol 29:23–43. [PubMed]
343. Turley SJ, Fletcher AL, Elpek KG. 2010. The stromal and haematopoietic antigen-presenting cells that reside in secondary lymphoid organs. Nat Rev Immunol 10:813–825. [PubMed]
344. Shiow LR, Rosen DB, Brdicková N, Xu Y, An J, Lanier LL, Cyster JG, Matloubian M. 2006. CD69 acts downstream of interferon-α/β to inhibit S1P1 and lymphocyte egress from lymphoid organs. Nature 440:540–544. [PubMed]
345. Hampton HR, Chtanova T. 2016. The lymph node neutrophil. Semin Immunol 28:129–136. [PubMed]
346. Chakarov S, Fazilleau N. 2014. Monocyte-derived dendritic cells promote T follicular helper cell differentiation. EMBO Mol Med 6:590–603. [PubMed]
347. Johansson-Lindbom B, Svensson M, Pabst O, Palmqvist C, Marquez G, Förster R, Agace WW. 2005. Functional specialization of gut CD103+ dendritic cells in the regulation of tissue-selective T cell homing. J Exp Med 202:1063–1073. [PubMed]
348. Annunziato F, Romagnani C, Romagnani S. 2015. The 3 major types of innate and adaptive cell-mediated effector immunity. J Allergy Clin Immunol 135:626–635. [PubMed]
349. Raphael I, Nalawade S, Eagar TN, Forsthuber TG. 2015. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine 74:5–17. [PubMed]
350. Weinmann AS. 2014. Roles for helper T cell lineage-specifying transcription factors in cellular specialization. Adv Immunol 124:171–206. [PubMed]
351. Arens R, Schoenberger SP. 2010. Plasticity in programming of effector and memory CD8 T-cell formation. Immunol Rev 235:190–205. [PubMed]
352. Peixoto A, Evaristo C, Munitic I, Monteiro M, Charbit A, Rocha B, Veiga-Fernandes H. 2007. CD8 single-cell gene coexpression reveals three different effector types present at distinct phases of the immune response. J Exp Med 204:1193–1205. [PubMed]
353. Monteiro M, Evaristo C, Legrand A, Nicoletti A, Rocha B. 2007. Cartography of gene expression in CD8 single cells: novel CCR7 subsets suggest differentiation independent of CD45RA expression. Blood 109:2863–2870. [PubMed]
354. Buchholz VR, Schumacher TN, Busch DH. 2016. T cell fate at the single-cell level. Annu Rev Immunol 34:65–92. [PubMed]
355. Shin H, Iwasaki A. 2013. Tissue-resident memory T cells. Immunol Rev 255:165–181. [PubMed]
356. Kastenmüller W, Brandes M, Wang Z, Herz J, Egen JG, Germain RN. 2013. Peripheral prepositioning and local CXCL9 chemokine-mediated guidance orchestrate rapid memory CD8+ T cell responses in the lymph node. Immunity 38:502–513. [PubMed]
357. Alexandre YO, Ghilas S, Sanchez C, Le Bon A, Crozat K, Dalod M. 2016. XCR1+ dendritic cells promote memory CD8+ T cell recall upon secondary infections with Listeria monocytogenes or certain viruses. J Exp Med 213:75–92. [PubMed]
358. Wakim LM, Waithman J, van Rooijen N, Heath WR, Carbone FR. 2008. Dendritic cell-induced memory T cell activation in nonlymphoid tissues. Science 319:198–202. [PubMed]
359. Ángeles Esteban M. 2012. An overview of the immunological defenses in fish skin. ISRN Immunol 2012:1–29.
360. Han Q, Das S, Hirano M, Holland SJ, McCurley N, Guo P, Rosenberg CS, Boehm T, Cooper MD. 2015. Characterization of lamprey IL-17 family members and their receptors. J Immunol 195:5440–5451. [PubMed]
361. Lugo-Villarino G, Balla KM, Stachura DL, Bañuelos K, Werneck MBF, Traver D. 2010. Identification of dendritic antigen-presenting cells in the zebrafish. Proc Natl Acad Sci U S A 107:15850–15855. [PubMed]
362. Flajnik MF, Kasahara M. 2010. Origin and evolution of the adaptive immune system: genetic events and selective pressures. Nat Rev Genet 11:47–59. [PubMed]
363. Hirano M. 2015. Evolution of vertebrate adaptive immunity: immune cells and tissues, and AID/APOBEC cytidine deaminases. BioEssays 37:877–887. [PubMed]
364. Sun JC, Ugolini S, Vivier E. 2014. Immunological memory within the innate immune system. EMBO J 33:1295–1303. [PubMed]
365. Gross M, Salame TM, Jung S. 2015. Guardians of the gut—murine intestinal macrophages and dendritic cells. Front Immunol 6:254. doi:10.3389/fimmu.2015.00254. [PubMed]
366. Star B, Nederbragt AJ, Jentoft S, Grimholt U, Malmstrøm M, Gregers TF, Rounge TB, Paulsen J, Solbakken MH, Sharma A, Wetten OF, Lanzén A, Winer R, Knight J, Vogel JH, Aken B, Andersen O, Lagesen K, Tooming-Klunderud A, Edvardsen RB, Tina KG, Espelund M, Nepal C, Previti C, Karlsen BO, Moum T, Skage M, Berg PR, Gjøen T, Kuhl H, Thorsen J, Malde K, Reinhardt R, Du L, Johansen SD, Searle S, Lien S, Nilsen F, Jonassen I, Omholt SW, Stenseth NC, Jakobsen KS. 2011. The genome sequence of Atlantic cod reveals a unique immune system. Nature 477:207–210. [PubMed]
367. Kasahara M. 2007. The 2R hypothesis: an update. Curr Opin Immunol 19:547–552. [PubMed]
368. De Silva NS, Klein U. 2015. Dynamics of B cells in germinal centres. Nat Rev Immunol 15:137–148. [PubMed]
369. Dudda JC, Simon JC, Martin S. 2004. Dendritic cell immunization route determines CD8+ T cell trafficking to inflamed skin: role for tissue microenvironment and dendritic cells in establishment of T cell-homing subsets. J Immunol 172:857–863. [PubMed]
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/content/journal/microbiolspec/10.1128/microbiolspec.MCHD-0046-2016
2016-12-02
2017-08-22

Abstract:

The aim of this review is to provide a coherent framework for understanding dendritic cells (DCs). It has seven sections. The introduction provides an overview of the immune system and essential concepts, particularly for the nonspecialist reader. Next, the “History” section outlines the early evolution of ideas about DCs and highlights some sources of confusion that still exist today. The “Lineages” section then focuses on five different populations of DCs: two subsets of “classical” DCs, plasmacytoid DCs, monocyte-derived DCs, and Langerhans cells. It highlights some cellular and molecular specializations of each, and also notes other DC subsets that have been proposed. The following “Tissues” section discusses the distribution and behavior of different DC subsets within nonlymphoid and secondary lymphoid tissues that are connected by DC migration pathways between them. In the “Tolerance” section, the role of DCs in central and peripheral tolerance is considered, including their ability to drive the differentiation of different populations of regulatory T cells. In contrast, the “Immunity” section considers the roles of DCs in sensing of infection and tissue damage, the initiation of primary responses, the T-cell effector phase, and the induction of immunological memory. The concluding section provides some speculative ideas about the evolution of DCs. It also revisits earlier concepts of generation of diversity and clonal selection in terms of DCs driving the evolution of T-cell responses. Throughout, this review highlights certain areas of uncertainty and suggests some avenues for future investigation.

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