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Chapter 42 : Myeloid Cells in Asthma

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Abstract:

Asthma is clinically defined by variable airway obstruction that causes recurrent periods of shortness of breath, chest tightness, wheezing, and coughing. Patients also often have altered mucus production and have problems in expectorating sputa because of reduced viscosity of the mucus. One of the characteristic changes to lung physiology is the occurrence of bronchial hyperreactivity, which is defined as a tendency of the smooth muscle layer to contract to nonspecific stimuli like cold air or exercise, and measured in the lung function lab as increased bronchoconstriction to very low amounts of histamine or methacholine. We now realize that asthma is not one single disorder, but rather a syndrome or a spectrum of disease, characterized by endotypes that rely on distinct pathomechanisms and controlled by various adaptive or innate immune cells ( ). In early life, asthma is often allergic, driven by CD4 Th2 lymphocytes and associated with allergic comorbidity like atopic dermatitis and rhinitis. On histology, target organs often contain many eosinophils. In adult-onset asthma, almost half of the cases are not associated with allergy. Some of these patients have eosinophilic airway inflammation, whereas others have a neutrophil-predominant inflammation, a mixed neutrophil-eosinophil infiltration, or even pauci-immune disease. Important comorbidities are obesity, acid-reflux disease, and chronic rhinosinusitis ( ). Across all age groups, the presence of a more neutrophilic infiltrate is associated with more (therapy-resistant) severe disease, and it is possible that this disease variant relies more on interleukin-17 (IL-17)-producing Th17 cells ( ).

Citation: Lambrecht B, Persson E, Hammad H. 2017. Myeloid Cells in Asthma, p 739-757. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0053-2016
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Figures

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Figure 1

The early and late allergic response. This figure depicts the alterations in the airways, as well as the lung function alterations (measured as the amount of air being exhaled in 1 s in a forced expiratory maneuver, or FEV) in allergic patients before, during, and after an experimental allergen challenge. Before the challenge, the airways of asthmatics are hyperreactive (this does not always lead to reduced FEV). Minutes after allergen challenge, there is bronchoconstriction, and this is reflected by a drop in FEV that can sometimes be as much as 50% in very severe asthma attacks. This is called the early or immediate allergic response. After some 3 to 6 h, there is a second drop in FEV, this time accompanied by edema of the airway wall, cellular influx with inflammatory cells, and bronchoconstriction. This phase is called the late or delayed allergic response.

Citation: Lambrecht B, Persson E, Hammad H. 2017. Myeloid Cells in Asthma, p 739-757. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0053-2016
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Image of Figure 2
Figure 2

The cellular interplay of myeloid and lymphoid cells in allergic asthma. (Left) A first allergen exposure leads to activation of CD11b cDC2s. This activation is direct or indirect, because lung epithelial cells make cytokines like IL-1, IL-33, IL-25, TSLP, and GM-CSF that mature the DCs. The same cytokines also activate basophils and ILC2, which control immediate innate eosinophilia. After a few hours, DCs will also arrive in the draining mediastinal nodes, where they will polarize adaptive immune cells to become Th2, Th21, and Th17 cells. B cells will be induced to secrete IgE. (Right) A recall response to allergens, which occurs continuously in patients allergic to perennial allergens. Upon repeated encounter with allergens, tissue mast cells and basophils are armed with IgE and release immediate mediators into the lung tissue, causing bronchoconstriction and local edema. Monocyte-derived cells (DCs and activated macrophages) will also take up allergens via IgE and this time present these allergens locally to T effector cells and resident memory Th2 cells. These effector cells reach the lungs because of chemokine production by monocyte-derived cells. The effector lymphocytes will also produce loss of IL-5, which boosts the production of eosinophils. These eosinophils migrate into the lungs and cause damage to the lung epithelium. In some cases, particularly when there is a Th17 response, neutrophils also will accumulate in the lungs. PGD, prostaglandin D. Modified from reference , with permission.

Citation: Lambrecht B, Persson E, Hammad H. 2017. Myeloid Cells in Asthma, p 739-757. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0053-2016
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References

/content/book/10.1128/9781555819194.chap42
1. Moore WC,, Hastie AT,, Li X,, Li H,, Busse WW,, Jarjour NN,, Wenzel SE,, Peters SP,, Meyers DA,, Bleecker ER . 2014. Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis. J Allergy Clin Immunol 133 : 15571563.e5. doi:10.1016/j.jaci.2013.10.011.
2. Wenzel SE . 2012. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 18 : 716725.
3. Lambrecht BN,, Hammad H . 2015. The immunology of asthma. Nat Immunol 16 : 4556.
4. Anderson GP . 2008. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet 372 : 11071119.
5. Lotvall J,, Akdis CA,, Bacharier LB,, Bjermer L,, Casale TB,, Custovic A,, Lemanske RF Jr,, Wardlaw AJ,, Wenzel SE,, Greenberger PA . 2011. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol 127 : 355360.
6. Wu W,, Bleecker E,, Moore W,, Busse WW,, Castro M,, Chung KF,, Calhoun WJ,, Erzurum S,, Gaston B,, Israel E,, Curran-Everett D,, Wenzel SE . 2014. Unsupervised phenotyping of Severe Asthma Research Program participants using expanded lung data. J Allergy Clin Immunol 133 : 12801288.
7. Mjösberg JM,, Trifari S,, Crellin NK,, Peters CP,, van Drunen CM,, Piet B,, Fokkens WJ,, Cupedo T,, Spits H . 2011. Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. Nat Immunol 12 : 10551062.
8. Mjösberg J,, Bernink J,, Golebski K,, Karrich JJ,, Peters CP,, Blom B,, te Velde AA,, Fokkens WJ,, van Drunen CM,, Spits H . 2012. The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells. Immunity 37 : 649659.
9. Hammad H,, Lambrecht BN . 2015. Barrier epithelial cells and the control of type 2 immunity. Immunity 43 : 2940.
10. Lambrecht BN,, Galli SJ . 2015. SnapShot: Integrated Type 2 Immune Responses. Immunity 43 : 408408.e1. doi:10.1016/j.immuni.2015.07.019.
11. Guilliams M,, Dutertre CA,, Scott CL,, McGovern N,, Sichien D,, Chakarov S,, Van Gassen S,, Chen J,, Poidinger M,, De Prijck S,, Tavernier SJ,, Low I,, Irac SE,, Mattar CN,, Sumatoh HR,, Low GH,, Chung TJ,, Chan DK,, Tan KK,, Hon TL,, Fossum E,, Bogen B,, Choolani M,, Chan JK,, Larbi A,, Luche H,, Henri S,, Saeys Y,, Newell EW,, Lambrecht BN,, Malissen B,, Ginhoux F . 2016. Unsupervised high-dimensional analysis aligns dendritic cells across tissues and species. Immunity 45 : 669684.
12. Sichien D,, Scott CL,, Martens L,, Vanderkerken M,, Van Gassen S,, Plantinga M,, Joeris T,, De Prijck S,, Vanhoutte L,, Vanheerswynghels M,, Van Isterdael G,, Toussaint W,, Madeira FB,, Vergote K,, Agace WW,, Clausen BE,, Hammad H,, Dalod M,, Saeys Y,, Lambrecht BN,, Guilliams M . 2016. IRF8 transcription factor controls survival and function of terminally differentiated conventional and plasmacytoid dendritic cells, respectively. Immunity 45 : 626640.
13. Scott CL,, Soen B,, Martens L,, Skrypek N,, Saelens W,, Taminau J,, Blancke G,, Van Isterdael G,, Huylebroeck D,, Haigh J,, Saeys Y,, Guilliams M,, Lambrecht BN,, Berx G . 2016. The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2. J Exp Med 213 : 897911.
14. Desch AN,, Gibbings SL,, Goyal R,, Kolde R,, Bednarek J,, Bruno T,, Slansky JE,, Jacobelli J,, Mason R,, Ito Y,, Messier E,, Randolph GJ,, Prabagar M,, Atif SM,, Segura E,, Xavier RJ,, Bratton DL,, Janssen WJ,, Henson PM,, Jakubzick CV . 2016. Flow cytometric analysis of mononuclear phagocytes in nondiseased human lung and lung-draining lymph nodes. Am J Respir Crit Care Med 193 : 614626.
15. Lambrecht BN,, Hammad H . 2012. Lung dendritic cells in respiratory viral infection and asthma: from protection to immunopathology. Annu Rev Immunol 30 : 243270.
16. Tang H,, Cao W,, Kasturi SP,, Ravindran R,, Nakaya HI,, Kundu K,, Murthy N,, Kepler TB,, Malissen B,, Pulendran B . 2010. The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling. Nat Immunol 11 : 608617.
17. Kumamoto Y,, Linehan M,, Weinstein JS,, Laidlaw BJ,, Craft JE,, Iwasaki A . 2013. CD301b+ dermal dendritic cells drive T helper 2 cell-mediated immunity. Immunity 39 : 733743.
18. Gao Y,, Nish SA,, Jiang R,, Hou L,, Licona-Limon P,, Weinstein JS,, Zhao H,, Medzhitov R . 2013. Control of T helper 2 responses by transcription factor IRF4-dependent dendritic cells. Immunity 39 : 722732.
19. Lambrecht BN,, De Veerman M,, Coyle AJ,, Gutierrez-Ramos JC,, Thielemans K,, Pauwels RA . 2000. Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation. J Clin Invest 106 : 551559.
20. Raymond M,, Van VQ,, Wakahara K,, Rubio M,, Sarfati M . 2011. Lung dendritic cells induce TH17 cells that produce TH2 cytokines, express GATA-3, and promote airway inflammation. J Allergy Clin Immunol 128 : 192201.e.6. doi:10.1016/j.jaci.2011.04.029.
21. van Rijt LS,, Vos N,, Willart M,, Muskens F,, Tak PP,, van der Horst C,, Hoogsteden HC,, Lambrecht BN . 2011. Persistent activation of dendritic cells after resolution of allergic airway inflammation breaks tolerance to inhaled allergens in mice. Am J Respir Crit Care Med 184 : 303311.
22. Krishnamoorthy N,, Oriss TB,, Paglia M,, Fei M,, Yarlagadda M,, Vanhaesebroeck B,, Ray A,, Ray P . 2008. Activation of c-Kit in dendritic cells regulates T helper cell differentiation and allergic asthma. Nat Med 14 : 565573.
23. 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 : 322335.
24. Hammad H,, Plantinga M,, Deswarte K,, Pouliot P,, Willart MA,, Kool M,, Muskens F,, Lambrecht BN . 2010. Inflammatory dendritic cells—not basophils—are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen. J Exp Med 207 : 20972111.
25. Phythian-Adams AT,, Cook PC,, Lundie RJ,, Jones LH,, Smith KA,, Barr TA,, Hochweller K,, Anderton SM,, Hammerling GJ,, Maizels RM,, MacDonald AS . 2010. CD11c depletion severely disrupts Th2 induction and development in vivo. J Exp Med 207 : 20892096.
26. De Kleer I,, Kool M,, de Bruijn M,, Willart M,, Van Moorleghem J,, Schuijs M,, Plantinga M,, Beyaert R,, Hams E,, Fallon GP,, Hammad H,, Hendriks R,, Lambrecht BN . 2016. Perinatal activation of the interleukin-33 pathway promotes type 2 immunity in the developing lung. Immunity doi:10.1016/j.immuni.2016.1010.1031.
27. Williams JW,, Tjota MY,, Clay BS,, Vander Lugt B,, Bandukwala HS,, Hrusch CL,, Decker DC,, Blaine KM,, Fixsen BR,, Singh H,, Sciammas R,, Sperling AI . 2013. Transcription factor IRF4 drives dendritic cells to promote Th2 differentiation. Nat Commun 4 : 2990. doi:10.1038/ncomms3990.
28. Kool M,, van Nimwegen M,, Willart MA,, Muskens F,, Boon L,, Smit JJ,, Coyle A,, Clausen BE,, Hoogsteden HC,, Lambrecht BN,, Hammad H . 2009. An anti-inflammatory role for plasmacytoid dendritic cells in allergic airway inflammation. J Immunol 183 : 10741082.
29. de Heer HJ,, Hammad H,, Soullie T,, Hijdra D,, Vos N,, Willart MA,, Hoogsteden HC,, Lambrecht BN . 2004. Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J Exp Med 200 : 8998.
30. Lombardi V,, Speak AO,, Kerzerho J,, Szely N,, Akbari O . 2012. CD8α+β and CD8α+β+ plasmacytoid dendritic cells induce Foxp3+ regulatory T cells and prevent the induction of airway hyper-reactivity. Mucosal Immunol 5 : 432443.
31. Hammad H,, Chieppa M,, Perros F,, Willart MA,, Germain RN,, Lambrecht BN . 2009. House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat Med 15 : 410416.
32. Willart MA,, Deswarte K,, Pouliot P,, Braun H,, Beyaert R,, Lambrecht BN,, Hammad H . 2012. Interleukin-1α controls allergic sensitization to inhaled house dust mite via the epithelial release of GM-CSF and IL-33. J Exp Med 209 : 15051517.
33. Lambrecht BN,, Hammad H . 2013. Asthma: the importance of dysregulated barrier immunity. Eur J Immunol 43 : 31253137.
34. Lambrecht BN,, Hammad H . 2014. Dendritic cell and epithelial cell interactions at the origin of murine asthma. Ann Am Thorac Soc 11(Suppl 5): S236S243.
35. Van Dyken SJ,, Nussbaum JC,, Lee J,, Molofsky AB,, Liang HE,, Pollack JL,, Gate RE,, Haliburton GE,, Ye CJ,, Marson A,, Erle DJ,, Locksley RM . 2016. A tissue checkpoint regulates type 2 immunity. Nat Immunol 17 : 13811387.
36. Schuijs MJ,, Willart MA,, Vergote K,, Gras D,, Deswarte K,, Ege MJ,, Madeira FB,, Beyaert R,, van Loo G,, Bracher F,, von Mutius E,, Chanez P,, Lambrecht BN,, Hammad H . 2015. Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells. Science 349 : 11061110.
37. Lee YG,, Jeong JJ,, Nyenhuis S,, Berdyshev E,, Chung S,, Ranjan R,, Karpurapu M,, Deng J,, Qian F,, Kelly EA,, Jarjour NN,, Ackerman SJ,, Natarajan V,, Christman JW,, Park GY . 2015. Recruited alveolar macrophages, in response to airway epithelial-derived monocyte chemoattractant protein 1/CCl2, regulate airway inflammation and remodeling in allergic asthma. Am J Respir Cell Mol Biol 52 : 772784.
38. Moniuszko M,, Bodzenta-Lukaszyk A,, Kowal K,, Lenczewska D,, Dabrowska M . 2009. Enhanced frequencies of CD14++CD16+, but not CD14+CD16+, peripheral blood monocytes in severe asthmatic patients. Clin Immunol 130 : 338346.
39. Zaslona Z,, Przybranowski S,, Wilke C,, van Rooijen N,, Teitz-Tennenbaum S,, Osterholzer JJ,, Wilkinson JE,, Moore BB,, Peters-Golden M . 2014. Resident alveolar macrophages suppress, whereas recruited monocytes promote, allergic lung inflammation in murine models of asthma. J Immunol 193 : 42454253.
40. Wu X,, Briseno CG,, Durai V,, Albring JC,, Haldar M,, Bagadia P,, Kim KW,, Randolph GJ,, Murphy TL,, Murphy KM . 2016. Mafb lineage tracing to distinguish macrophages from other immune lineages reveals dual identity of Langerhans cells. J Exp Med 213 : 25532565.
41. van Rijt LS,, Jung S,, Kleinjan A,, Vos N,, Willart M,, Duez C,, Hoogsteden HC,, Lambrecht BN . 2005. In vivo depletion of lung CD11c+ dendritic cells during allergen challenge abrogates the characteristic features of asthma. J Exp Med 201 : 981991.
42. Lambrecht BN,, Salomon B,, Klatzmann D,, Pauwels RA . 1998. Dendritic cells are required for the development of chronic eosinophilic airway inflammation in response to inhaled antigen in sensitized mice. J Immunol 160 : 40904097.
43. Huber S,, Hoffmann R,, Muskens F,, Voehringer D . 2010. Alternatively activated macrophages inhibit T-cell proliferation by Stat6-dependent expression of PD-L2. Blood 116 : 33113320.
44. Huh JC,, Strickland DH,, Jahnsen FL,, Turner DJ,, Thomas JA,, Napoli S,, Tobagus I,, Stumbles PA,, Sly PD,, Holt PG . 2003. Bidirectional interactions between antigen-bearing respiratory tract dendritic cells (DCs) and T cells precede the late phase reaction in experimental asthma: DC activation occurs in the airway mucosa but not in the lung parenchyma. J Exp Med 198 : 1930.
45. 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 : 11831199.
46. Turner DL,, Bickham KL,, Thome JJ,, Kim CY,, D’Ovidio F,, Wherry EJ,, Farber DL . 2014. Lung niches for the generation and maintenance of tissue-resident memory T cells. Mucosal Immunol 7 : 501510.
47. Medoff BD,, Seung E,, Hong S,, Thomas SY,, Sandall BP,, Duffield JS,, Kuperman DA,, Erle DJ,, Luster AD . 2009. CD11b+ myeloid cells are the key mediators of Th2 cell homing into the airway in allergic inflammation. J Immunol 182 : 623635.
48. Sallmann E,, Reininger B,, Brandt S,, Duschek N,, Hoflehner E,, Garner-Spitzer E,, Platzer B,, Dehlink E,, Hammer M,, Holcmann M,, Oettgen HC,, Wiedermann U,, Sibilia M,, Fiebiger E,, Rot A,, Maurer D . 2011. High-affinity IgE receptors on dendritic cells exacerbate Th2-dependent inflammation. J Immunol 187 : 164171.
49. Tjota MY,, Williams JW,, Lu T,, Clay BS,, Byrd T,, Hrusch CL,, Decker DC,, de Araujo CA,, Bryce PJ,, Sperling AI . 2013. IL-33-dependent induction of allergic lung inflammation by FcγRIII signaling. J Clin Invest 123 : 22872297.
50. Nakano H,, Burgents JE,, Nakano K,, Whitehead GS,, Cheong C,, Bortner CD,, Cook DN . 2013. Migratory properties of pulmonary dendritic cells are determined by their developmental lineage. Mucosal Immunol 6 : 678691.
51. Parsons MW,, Li L,, Wallace AM,, Lee MJ,, Katz HR,, Fernandez JM,, Saijo S,, Iwakura Y,, Austen KF,, Kanaoka Y,, Barrett NA . 2014. Dectin-2 regulates the effector phase of house dust mite-elicited pulmonary inflammation independently from its role in sensitization. J Immunol 192 : 13611371.
52. Guilliams M,, De Kleer I,, Henri S,, Post S,, Vanhoutte L,, De Prijck S,, Deswarte K,, Malissen B,, Hammad H,, Lambrecht BN . 2013. Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF. J Exp Med 210 : 19771992.
53. van de Laar L,, Saelens W,, De Prijck S,, Martens L,, Scott CL,, Van Isterdael G,, Hoffmann E,, Beyaert R,, Saeys Y,, Lambrecht BN,, Guilliams M . 2016. Yolk sac macrophages, fetal liver, and adult monocytes can colonize an empty niche and develop into functional tissue-resident macrophages. Immunity 44 : 755768.
54. Westphalen K,, Gusarova GA,, Islam MN,, Subramanian M,, Cohen TS,, Prince AS,, Bhattacharya J . 2014. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity. Nature 506 : 503506.
55. Bhattacharya J,, Westphalen K . 2016. Macrophage-epithelial interactions in pulmonary alveoli. Semin Immunopathol 38 : 461469.
56. Thepen T,, McMenamin C,, Oliver J,, Kraal G,, Holt PG . 1991. Regulation of immune responses to inhaled antigen by alveolar macrophages (AM) : differential effects of AM elimination in vivo on the induction of tolerance versus immunity. Eur J Immunol 21 : 28452850.
57. Bilyk N,, Holt PG . 1993. Inhibition of the immunosuppressive activity of resident pulmonary alveolar macrophages by granulocyte/macrophage colony-stimulating factor. J Exp Med 177 : 17731777.
58. Holt PG,, Oliver J,, Bilyk N,, McMenamin C,, McMenamin PG,, Kraal G,, Thepen T . 1993. Downregulation of the antigen presenting cell function(s) of pulmonary dendritic cells in vivo by resident alveolar macrophages. J Exp Med 177 : 397407.
59. Bilyk N,, Holt PG . 1995. Cytokine modulation of the immunosuppressive phenotype of pulmonary alveolar macrophage populations. Immunology 86 : 231237.
60. Upham JW,, Strickland DH,, Bilyk N,, Robinson BW,, Holt PG . 1995. Alveolar macrophages from humans and rodents selectively inhibit T-cell proliferation but permit T-cell activation and cytokine secretion. Immunology 84 : 142147.
61. Tang C,, Inman MD,, van Rooijen N,, Yang P,, Shen H,, Matsumoto K,, O’Byrne PM . 2001. Th type 1-stimulating activity of lung macrophages inhibits Th2- mediated allergic airway inflammation by an IFN-γ-dependent mechanism. J Immunol 166 : 14711481.
62. Tang C,, Ward C,, Reid D,, Bish R,, O’Byrne PM,, Walters EH . 2001. Normally suppressing CD40 coregulatory signals delivered by airway macrophages to TH2 lymphocytes are defective in patients with atopic asthma. J Allergy Clin Immunol 107 : 863870.
63. Draijer C,, Boorsma CE,, Reker-Smit C,, Post E,, Poelstra K,, Melgert BN . 2016. PGE2-treated macrophages inhibit development of allergic lung inflammation in mice. J Leukoc Biol 100 : 95102.
64. Bourdonnay E,, Zaslona Z,, Penke LR,, Speth JM,, Schneider DJ,, Przybranowski S,, Swanson JA,, Mancuso P,, Freeman CM,, Curtis JL,, Peters-Golden M . 2015. Transcellular delivery of vesicular SOCS proteins from macrophages to epithelial cells blunts inflammatory signaling. J Exp Med 212 : 729742.
65. Speth JM,, Bourdonnay E,, Penke LR,, Mancuso P,, Moore BB,, Weinberg JB,, Peters-Golden M . 2016. Alveolar epithelial cell-derived prostaglandin E2 serves as a request signal for macrophage secretion of suppressor of cytokine signaling 3 during innate inflammation. J Immunol 196 : 51125120.
66. Bedoret D,, Wallemacq H,, Marichal T,, Desmet C,, Quesada Calvo F,, Henry E,, Closset R,, Dewals B,, Thielen C,, Gustin P,, de Leval L,, Van Rooijen N,, Le Moine A,, Vanderplasschen A,, Cataldo D,, Drion PV,, Moser M,, Lekeux P,, Bureau F . 2009. Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice. J Clin Invest 119 : 37233738.
67. Albacker LA,, Yu S,, Bedoret D,, Lee WL,, Umetsu SE,, Monahan S,, Freeman GJ,, Umetsu DT,, Dekruyff RH . 2013. TIM-4, expressed by medullary macrophages, regulates respiratory tolerance by mediating phagocytosis of antigen-specific T cells. Mucosal Immunol 6 : 580590.
68. Soroosh P,, Doherty TA,, Duan W,, Mehta AK,, Choi H,, Adams YF,, Mikulski Z,, Khorram N,, Rosenthal P,, Broide DH,, Croft M . 2013. Lung-resident tissue macrophages generate Foxp3+ regulatory T cells and promote airway tolerance. J Exp Med 210 : 775788.
69. Kurowska-Stolarska M,, Stolarski B,, Kewin P,, Murphy G,, Corrigan CJ,, Ying S,, Pitman N,, Mirchandani A,, Rana B,, van Rooijen N,, Shepherd M,, McSharry C,, McInnes IB,, Xu D,, Liew FY . 2009. IL-33 amplifies the polarization of alternatively activated macrophages that contribute to airway inflammation. J Immunol 183 : 64696477.
70. Byers DE,, Holtzman MJ . 2011. Alternatively activated macrophages and airway disease. Chest 140 : 768774.
71. Ford AQ,, Dasgupta P,, Mikhailenko I,, Smith EM,, Noben-Trauth N,, Keegan AD . 2012. Adoptive transfer of IL-4Rα+ macrophages is sufficient to enhance eosinophilic inflammation in a mouse model of allergic lung inflammation. BMC Immunol 13 : 6. doi:10.1186/1471-2172-13-6.
72. Nieuwenhuizen NE,, Kirstein F,, Jayakumar J,, Emedi B,, Hurdayal R,, Horsnell WG,, Lopata AL,, Brombacher F . 2012. Allergic airway disease is unaffected by the absence of IL-4Rα-dependent alternatively activated macrophages. J Allergy Clin Immunol 130 : 743750 e748.
73. Han H,, Headley MB,, Xu W,, Comeau MR,, Zhou B,, Ziegler SF . 2013. Thymic stromal lymphopoietin amplifies the differentiation of alternatively activated macrophages. J Immunol 190 : 904912.
74. Robbe P,, Draijer C,, Borg TR,, Luinge M,, Timens W,, Wouters IM,, Melgert BN,, Hylkema MN . 2015. Distinct macrophage phenotypes in allergic and nonallergic lung inflammation. Am J Physiol Lung Cell Mol Physiol 308 : L358L367.
75. Moreira AP,, Cavassani KA,, Hullinger R,, Rosada RS,, Fong DJ,, Murray L,, Hesson DP,, Hogaboam CM . 2010. Serum amyloid P attenuates M2 macrophage activation and protects against fungal spore-induced allergic airway disease. J Allergy Clin Immunol 126 : 712721.e7. doi:10.1016/j.jaci.2010.06.010.
76. Braza F,, Dirou S,, Forest V,, Sauzeau V,, Hassoun D,, Chesne J,, Cheminant-Muller MA,, Sagan C,, Magnan A,, Lemarchand P . 2016. Mesenchymal stem cells induce suppressive macrophages through phagocytosis in a mouse model of asthma. Stem Cells 34 : 18361845.
77. Jaffar ZH,, Roberts K,, Pandit A,, Linsley P,, Djukanovic R,, Holgate ST . 1999. B7 costimulation is required for IL-5 and IL-13 secretion by bronchial biopsy tissue of atopic asthmatic subjects in response to allergen stimulation. Am J Respir Cell Mol Biol 20 : 153162.
78. Girodet PO,, Nguyen D,, Mancini JD,, Hundal M,, Zhou X,, Israel E,, Cernadas M . 2016. Alternative macrophage activation is increased in asthma. Am J Respir Cell Mol Biol 55 : 467475.
79. Staples KJ,, Hinks TS,, Ward JA,, Gunn V,, Smith C,, Djukanović R . 2012. Phenotypic characterization of lung macrophages in asthmatic patients: overexpression of CCL17. J Allergy Clin Immunol 130 : 14041412.e7. doi:10.1016/j.jaci.2012.07.023.
80. Melgert BN,, ten Hacken NH,, Rutgers B,, Timens W,, Postma DS,, Hylkema MN . 2011. More alternative activation of macrophages in lungs of asthmatic patients. J Allergy Clin Immunol 127 : 831833.
81. Martinez FO,, Helming L,, Milde R,, Varin A,, Melgert BN,, Draijer C,, Thomas B,, Fabbri M,, Crawshaw A,, Ho LP,, Ten Hacken NH,, Cobos Jiménez V,, Kootstra NA,, Hamann J,, Greaves DR,, Locati M,, Mantovani A,, Gordon S . 2013. Genetic programs expressed in resting and IL-4 alternatively activated mouse and human macrophages: similarities and differences. Blood 121 : e57e69. doi:10.1182/blood-2012-06-436212.
82. Melgert BN,, Oriss TB,, Qi Z,, Dixon-McCarthy B,, Geerlings M,, Hylkema MN,, Ray A . 2010. Macrophages: regulators of sex differences in asthma? Am J Respir Cell Mol Biol 42 : 595603.
83. Bousquet J,, Chanez P,, Lacoste JY,, Barneon G,, Ghavanian N,, Enander P,, Venge P,, Ahlstedt S,, Simony-Lafontaine J,, Godard P . 1990. Eosinophilic inflammation in asthma. N Engl J Med 323 : 10331039.
84. Travers J,, Rothenberg ME . 2015. Eosinophils in mucosal immune responses. Mucosal Immunol 8 : 464475.
85. Possa SS,, Leick EA,, Prado CM,, Martins MA,, Tibério IF . 2013. Eosinophilic inflammation in allergic asthma. Front Pharmacol 4 : 46. doi:10.3389/fphar.2013.00046.
86. Chu DK,, Jimenez-Saiz R,, Verschoor CP,, Walker TD,, Goncharova S,, Llop-Guevara A,, Shen P,, Gordon ME,, Barra NG,, Bassett JD,, Kong J,, Fattouh R,, McCoy KD,, Bowdish DM,, Erjefalt JS,, Pabst O,, Humbles AA,, Kolbeck R,, Waserman S,, Jordana M . 2014. Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo. J Exp Med 211 : 16571672.
87. Chu VT,, Frohlich A,, Steinhauser G,, Scheel T,, Roch T,, Fillatreau S,, Lee JJ,, Lohning M,, Berek C . 2011. Eosinophils are required for the maintenance of plasma cells in the bone marrow. Nat Immunol 12 : 151159.
88. Brusselle GG,, Kips JC,, Tavernier J,, Van Der Heyden JG,, Cuvelier CA,, Pauwels RA,, Bluethmann H . 1994. Attenuation of allergic airway inflammation in IL-4 deficient mice. Clin Exp Allergy 24 : 7380.
89. Bousquet J,, Chanez P,, Lacoste JY,, Barnéon G,, Ghavanian N,, Enander I,, Venge P,, Ahlstedt S,, Simony-Lafontaine J,, Godard P,, Michel FB . 1990. Eosinophilic inflammation in asthma. N Engl J Med 323 : 10331039.
90. Jatakanon A,, Lim S,, Barnes PJ . 2000. Changes in sputum eosinophils predict loss of asthma control. Am J Respir Crit Care Med 161 : 6472.
91. Deykin A,, Lazarus SC,, Fahy JV,, Wechsler ME,, Boushey HA,, Chinchilli VM,, Craig TJ,, Dimango E,, Kraft M,, Leone F,, Lemanske RF,, Martin RJ,, Pesola GR,, Peters SP,, Sorkness CA,, Szefler SJ,, Israel E ; Asthma Clinical Research Network, National Heart, Lung, and Blood Institute/NIH . 2005. Sputum eosinophil counts predict asthma control after discontinuation of inhaled corticosteroids. J Allergy Clin Immunol 115 : 720727.
92. Jacobsen EA,, Lee NA,, Lee JJ . 2014. Re-defining the unique roles for eosinophils in allergic respiratory inflammation. Clin Exp Allergy 44 : 11191136.
93. Mori Y,, Iwasaki H,, Kohno K,, Yoshimoto G,, Kikushige Y,, Okeda A,, Uike N,, Niiro H,, Takenaka K,, Nagafuji K,, Miyamoto T,, Harada M,, Takatsu K,, Akashi K . 2009. Identification of the human eosinophil lineage-committed progenitor: revision of phenotypic definition of the human common myeloid progenitor. J Exp Med 206 : 183193.
94. Iwasaki H,, Mizuno S,, Mayfield R,, Shigematsu H,, Arinobu Y,, Seed B,, Gurish MF,, Takatsu K,, Akashi K . 2005. Identification of eosinophil lineage-committed progenitors in the murine bone marrow. J Exp Med 201 : 18911897.
95. Tsuzuki H,, Arinobu Y,, Miyawaki K,, Takaki A,, Ota SI,, Ota Y,, Mitoma H,, Akahoshi M,, Mori Y,, Iwasaki H,, Niiro H,, Tsukamoto H,, Akashi K . 2017. Functional IL-33 receptors are expressed in early progenitor stages of allergy-related granulocytes. Immunology 150 : 6473.
96. Lopez AF,, Begley CG,, Williamson DJ,, Warren DJ,, Vadas MA,, Sanderson CJ . 1986. Murine eosinophil differentiation factor. An eosinophil-specific colony-stimulating factor with activity for human cells. J Exp Med 163 : 10851099.
97. Asquith KL,, Ramshaw HS,, Hansbro PM,, Beagley KW,, Lopez AF,, Foster PS . 2008. The IL-3/IL-5/GM-CSF common receptor plays a pivotal role in the regulation of Th2 immunity and allergic airway inflammation. J Immunol 180 : 11991206.
98. Kopf M,, Brombacher F,, Hodgkin PD,, Ramsay AJ,, Milbourne EA,, Dai WJ,, Ovington KS,, Behm CA,, Kohler G,, Young IG,, Matthaei KI . 1996. IL-5-deficient mice have a developmental defect in CD5+ B-1 cells and lack eosinophilia but have normal antibody and cytotoxic T cell responses. Immunity 4 : 1524.
99. Nakajima H,, Iwamoto I,, Tomoe S,, Matsumura R,, Tomioka H,, Takatsu K,, Yoshida S . 1992. CD4+ T-lymphocytes and interleukin-5 mediate antigen-induced eosinophil infiltration into the mouse trachea. Am Rev Respir Dis 146 : 374377.
100. Yoshida T,, Ikuta K,, Sugaya H,, Maki K,, Takagi M,, Kanazawa H,, Sunaga S,, Kinashi T,, Yoshimura K,, Miyazaki J,, Takaki S,, Takatsu K . 1996. Defective B-1 cell development and impaired immunity against Angiostrongylus cantonensis in IL-5Rα-deficient mice. Immunity 4 : 483494.
101. Dent LA,, Strath M,, Mellor AL,, Sanderson CJ . 1990. Eosinophilia in transgenic mice expressing interleukin 5. J Exp Med 172 : 14251431.
102. Leckie MJ,, ten Brinke A,, Khan J,, Diamant Z,, O’Connor BJ,, Walls CM,, Mathur AK,, Cowley HC,, Chung KF,, Djukanovic R,, Hansel TT,, Holgate ST,, Sterk PJ,, Barnes PJ . 2000. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 356 : 21442148.
103. Flood-Page P,, Menzies-Gow A,, Phipps S,, Ying S,, Wangoo A,, Ludwig MS,, Barnes N,, Robinson D,, Kay AB . 2003. Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics. J Clin Invest 112 : 10291036.
104. Menzies-Gow A,, Flood-Page P,, Sehmi R,, Burman J,, Hamid Q,, Robinson DS,, Kay AB,, Denburg J . 2003. Anti-IL-5 (mepolizumab) therapy induces bone marrow eosinophil maturational arrest and decreases eosinophil progenitors in the bronchial mucosa of atopic asthmatics. J Allergy Clin Immunol 111 : 714719.
105. Garrett JK,, Jameson SC,, Thomson B,, Collins MH,, Wagoner LE,, Freese DK,, Beck LA,, Boyce JA,, Filipovich AH,, Villanueva JM,, Sutton SA,, Assa’ad AH,, Rothenberg ME . 2004. Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes. J Allergy Clin Immunol 113 : 115119.
106. Phipps S,, Flood-Page P,, Menzies-Gow A,, Ong YE,, Kay AB . 2004. Intravenous anti-IL-5 monoclonal antibody reduces eosinophils and tenascin deposition in allergen-challenged human atopic skin. J Invest Dermatol 122 : 14061412.
107. Stein ML,, Villanueva JM,, Buckmeier BK,, Yamada Y,, Filipovich AH,, Assa’ad AH,, Rothenberg ME . 2008. Anti-IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels. J Allergy Clin Immunol 121 : 14731483.
108. Haldar P,, Brightling CE,, Hargadon B,, Gupta S,, Monteiro W,, Sousa A,, Marshall RP,, Bradding P,, Green RH,, Wardlaw AJ,, Pavord ID . 2009. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 360 : 973984.
109. Roufosse FE,, Kahn JE,, Gleich GJ,, Schwartz LB,, Singh AD,, Rosenwasser LJ,, Denburg JA,, Ring J,, Rothenberg ME,, Sheikh J,, Haig AE,, Mallett SA,, Templeton DN,, Ortega HG,, Klion AD . 2012. Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes. J Allergy Clin Immunol 131 : 461467.e5. doi:10.1016/j.jaci.2012.07.055.
110. Bel EH,, Wenzel SE,, Thompson PJ,, Prazma CM,, Keene ON,, Yancey SW,, Ortega HG,, Pavord ID . 2014. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 371 : 11891197.
111. Ortega HG,, Liu MC,, Pavord ID,, Brusselle GG,, FitzGerald JM,, Chetta A,, Humbert M,, Katz LE,, Keene ON,, Yancey SW,, Chanez P , MENSA Investigators . 2014. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 371 : 11981207.
112. Yu C,, Cantor AB,, Yang H,, Browne C,, Wells RA,, Fujiwara Y,, Orkin SH . 2002. Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo. J Exp Med 195 : 13871395.
113. Southam DS,, Widmer N,, Ellis R,, Hirota JA,, Inman MD,, Sehmi R . 2005. Increased eosinophil-lineage committed progenitors in the lung of allergen-challenged mice. J Allergy Clin Immunol 115 : 95102.
114. Sehmi R,, Smith SG,, Kjarsgaard M,, Radford K,, Boulet LP,, Lemiere C,, Prazma CM,, Ortega H,, Martin JG,, Nair P . 2016. Role of local eosinophilopoietic processes in the development of airway eosinophilia in prednisone-dependent severe asthma. Clin Exp Allergy 46 : 793802.
115. Foster PS,, Mould AW,, Yang M,, Mackenzie J,, Mattes J,, Hogan SP,, Mahalingam S,, McKenzie AN,, Rothenberg ME,, Young IG,, Matthaei KI,, Webb DC . 2001. Elemental signals regulating eosinophil accumulation in the lung. Immunol Rev 179 : 173181.
116. MacKenzie JR,, Mattes J,, Dent LA,, Foster PS . 2001. Eosinophils promote allergic disease of the lung by regulating CD4+ Th2 lymphocyte function. J Immunol 167 : 31463155.
117. Foster PS,, Hogan SP,, Yang M,, Mattes J,, Young IG,, Matthaei KI,, Kumar RK,, Mahalingam S,, Webb DC . 2002. Interleukin-5 and eosinophils as therapeutic targets for asthma. Trends Mol Med 8 : 162167.
118. Mattes J,, Yang M,, Mahalingam S,, Kuehr J,, Webb DC,, Simson L,, Hogan SP,, Koskinen A,, McKenzie AN,, Dent LA,, Rothenberg ME,, Matthaei KI,, Young IG,, Foster PS . 2002. Intrinsic defect in T cell production of interleukin (IL)-13 in the absence of both IL-5 and eotaxin precludes the development of eosinophilia and airways hyperreactivity in experimental asthma. J Exp Med 195 : 14331444.
119. Rothenberg ME,, Luster AD,, Leder P . 1995. Murine eotaxin: an eosinophil chemoattractant inducible in endothelial cells and in interleukin 4-induced tumor suppression. Proc Natl Acad Sci U S A 92 : 89608964.
120. Rothenberg ME,, Luster AD,, Lilly CM,, Drazen JM,, Leder P . 1995. Constitutive and allergen-induced expression of eotaxin mRNA in the guinea pig lung. J Exp Med 181 : 12111216.
121. Garcia-Zepeda EA,, Rothenberg ME,, Ownbey RT,, Celestin J,, Leder P,, Luster AD . 1996. Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia. Nat Med 2 : 449456.
122. Rothenberg ME,, MacLean JA,, Pearlman E,, Luster AD,, Leder P . 1997. Targeted disruption of the chemokine eotaxin partially reduces antigen-induced tissue eosinophilia. J Exp Med 185 : 785790.
123. Hogan SP,, Mould AW,, Young JM,, Rothenberg ME,, Ramsay AJ,, Matthaei K,, Young IG,, Foster PS . 1998. Cellular and molecular regulation of eosinophil trafficking to the lung. Immunol Cell Biol 76 : 454460.
124. Mould AW,, Ramsay AJ,, Matthaei KI,, Young IG,, Rothenberg ME,, Foster PS . 2000. The effect of IL-5 and eotaxin expression in the lung on eosinophil trafficking and degranulation and the induction of bronchial hyperreactivity. J Immunol 164 : 21422150.
125. Zimmermann N,, Hershey GK,, Foster PS,, Rothenberg ME . 2003. Chemokines in asthma: cooperative interaction between chemokines and IL-13. J Allergy Clin Immunol 111 : 227242; quiz 243.
126. Fulkerson PC,, Fischetti CA,, Rothenberg ME . 2006. Eosinophils and CCR3 regulate interleukin-13 transgene-induced pulmonary remodeling. Am J Pathol 169 : 21172126.
127. Ravensberg AJ,, Ricciardolo FL,, van Schadewijk A,, Rabe KF,, Sterk PJ,, Hiemstra PS,, Mauad T . 2005. Eotaxin-2 and eotaxin-3 expression is associated with persistent eosinophilic bronchial inflammation in patients with asthma after allergen challenge. J Allergy Clin Immunol 115 : 779785.
128. Ying S,, Robinson DS,, Meng Q,, Rottman J,, Kennedy R,, Ringler DJ,, Mackay CR,, Daugherty BL,, Springer MS,, Durham SR,, Williams TJ,, Kay AB . 1997. Enhanced expression of eotaxin and CCR3 mRNA and protein in atopic asthma. Association with airway hyperresponsiveness and predominant co-localization of eotaxin mRNA to bronchial epithelial and endothelial cells. Eur J Immunol 27 : 35073516.
129. Ganzalo JA,, Jia GQ,, Aguirre V,, Friend D,, Coyle AJ,, Jenkins NA,, Lin GS,, Katz H,, Lichtman A,, Copeland N,, Kopf M,, Gutierrez-Ramos JC . 1996. Mouse Eotaxin expression parallels eosinophil accumulation during lung allergic inflammation but it is not restricted to a Th2-type response. Immunity 4 : 114.
130. Gonzalo JA,, Lloyd CM,, Wen D,, Albar JP,, Wells TN,, Proudfoot A,, Martinez-A C,, Dorf M,, Bjerke T,, Coyle AJ,, Gutierrez-Ramos JC . 1998. The coordinated action of CC chemokines in the lung orchestrates allergic inflammation and airway hyperresponsiveness. J Exp Med 188 : 157167.
131. Tsuyuki S,, Bertrand C,, Erard F,, Trifilieff A,, Tsuyuki J,, Wesp M,, Anderson GP,, Coyle AJ . 1995. Activation of the Fas receptor on lung eosinophils leads to apoptosis and the resolution of eosinophilic inflammation of the airways. J Clin Invest 96 : 29242931.
132. Park YM,, Bochner BS . 2010. Eosinophil survival and apoptosis in health and disease. Allergy Asthma Immunol Res 2 : 87101.
133. Kolbeck R,, Kozhich A,, Koike M,, Peng L,, Andersson CK,, Damschroder MM,, Reed JL,, Woods R,, Dall’acqua WW,, Stephens GL,, Erjefalt JS,, Bjermer L,, Humbles AA,, Gossage D,, Wu H,, Kiener PA,, Spitalny GL,, Mackay CR,, Molfino NA,, Coyle AJ . 2010. MEDI-563, a humanized anti-IL-5 receptor α mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol 125 : 13441353.e2. doi:10.1016/j.jaci.2010.04.004.
134. Bagley CJ,, Lopez AF,, Vadas MA . 1997. New frontiers for IL-5. J Allergy Clin Immunol 99 : 725728.
135. Coyle AJ,, Ackerman SJ,, Irvin CG . 1993. Cationic proteins induce airway hyperresponsiveness dependent on charge interactions. Am Rev Respir Dis 147 : 896900.
136. Coyle AJ,, Perretti F,, Manzini S,, Irvin CG . 1994. Cationic protein-induced sensory nerve activation: role of substance P in airway hyperresponsiveness and plasma protein extravasation. J Clin Invest 94 : 23012306.
137. Coyle AJ,, Uchida D,, Ackerman SJ,, Mitzner W,, Irvin CG . 1994. Role of cationic proteins in the airway. Hyperresponsiveness due to airway inflammation. Am J Respir Crit Care Med 150 : S63S71.
138. Coyle AJ,, Ackerman SJ,, Burch R,, Proud D,, Irvin CG . 1995. Human eosinophil-granule major basic protein and synthetic polycations induce airway hyperresponsiveness in vivo dependent on bradykinin generation. J Clin Invest 95 : 17351740.
139. Jacoby DB,, Gleich GJ,, Fryer AD . 1993. Human eosinophil major basic protein is an endogenous allosteric antagonist at the inhibitory muscarinic M2 receptor. J Clin Invest 91 : 13141318.
140. Morshed M,, Yousefi S,, Stockle C,, Simon HU,, Simon D . 2012. Thymic stromal lymphopoietin stimulates the formation of eosinophil extracellular traps. Allergy 67 : 11271137.
141. Schorn C,, Janko C,, Latzko M,, Chaurio R,, Schett G,, Herrmann M . 2012. Monosodium urate crystals induce extracellular DNA traps in neutrophils, eosinophils, and basophils but not in mononuclear cells. Front Immunol 3 : 277. doi:10.3389/fimmu.2012.00277.
142. Yousefi S,, Simon D,, Simon HU . 2012. Eosinophil extracellular DNA traps: molecular mechanisms and potential roles in disease. Curr Opin Immunol 24 : 736739.
143. Ueki S,, Melo RC,, Ghiran I,, Spencer LA,, Dvorak AM,, Weller PF . 2013. Eosinophil extracellular DNA trap cell death mediates lytic release of free secretion-competent eosinophil granules in humans. Blood 121 : 20742083.
144. Simon D,, Radonjic-Hosli S,, Straumann A,, Yousefi S,, Simon HU . 2015. Active eosinophilic esophagitis is characterized by epithelial barrier defects and eosinophil extracellular trap formation. Allergy 70 : 443452.
145. Fulkerson PC,, Rothenberg ME . 2013. Targeting eosinophils in allergy, inflammation and beyond. Nat Rev Drug Discov 12 : 117129.
146. Henderson WR Jr,, Lewis DB,, Albert RK,, Zhang Y,, Lamm WJ,, Chiang GK,, Jones F,, Eriksen P,, Tien YT,, Jonas M,, Chi EY . 1996. The importance of leukotrienes in airway inflammation in a mouse model of asthma. J Exp Med 184 : 14831494.
147. Jacobsen EA,, Ochkur SI,, Pero RS,, Taranova AG,, Protheroe CA,, Colbert DC,, Lee NA,, Lee JJ . 2008. Allergic pulmonary inflammation in mice is dependent on eosinophil-induced recruitment of effector T cells. J Exp Med 205 : 699710.
148. Song DJ,, Cho JY,, Lee SY,, Miller M,, Rosenthal P,, Soroosh P,, Croft M,, Zhang M,, Varki A,, Broide DH . 2009. Anti-Siglec-F antibody reduces allergen-induced eosinophilic inflammation and airway remodeling. J Immunol 183 : 53335341.
149. Doyle AD,, Jacobsen EA,, Ochkur SI,, McGarry MP,, Shim KG,, Nguyen DT,, Protheroe C,, Colbert D,, Kloeber J,, Neely J,, Shim KP,, Dyer KD,, Rosenberg HF,, Lee JJ,, Lee NA . 2013. Expression of the secondary granule proteins major basic protein 1 (MBP-1) and eosinophil peroxidase (EPX) is required for eosinophilopoiesis in mice. Blood 122 : 781790.
150. Doyle AD,, Jacobsen EA,, Ochkur SI,, Willetts L,, Shim K,, Neely J,, Kloeber J,, Lesuer WE,, Pero RS,, Lacy P,, Moqbel R,, Lee NA,, Lee JJ . 2013. Homologous recombination into the eosinophil peroxidase locus generates a strain of mice expressing Cre recombinase exclusively in eosinophils. J Leukoc Biol 94 : 1724.
151. Jacobsen EA,, Doyle AD,, Colbert DC,, Zellner KR,, Protheroe CA,, LeSuer WE,, Lee NA,, Lee JJ . 2015. Differential activation of airway eosinophils induces IL-13-mediated allergic Th2 pulmonary responses in mice. Allergy 70 : 11481159.
152. Trifilieff A,, Fujitani Y,, Coyle AJ,, Kopf M,, Bertrand C . 2001. IL-5 deficiency abolishes aspects of airway remodelling in a murine model of lung inflammation. Clin Exp Allergy 31 : 934942.
153. Torrego A,, Hew M,, Oates T,, Sukkar M,, Fan Chung K . 2007. Expression and activation of TGF-β isoforms in acute allergen-induced remodelling in asthma. Thorax 62 : 307313.
154. Al Heialy S,, McGovern TK,, Martin JG . 2011. Insights into asthmatic airway remodelling through murine models. Respirology 16 : 589597.
155. Saglani S,, Lloyd CM . 2014. Eosinophils in the pathogenesis of paediatric severe asthma. Curr Opin Allergy Clin Immunol 14 : 143148.
156. Humbles AA,, Lloyd CM,, McMillan SJ,, Friend DS,, Xanthou G,, McKenna EE,, Ghiran S,, Gerard NP,, Yu C,, Orkin SH,, Gerard C . 2004. A critical role for eosinophils in allergic airways remodeling. Science 305 : 17761779.
157. Fattouh R,, Al-Garawi A,, Fattouh M,, Arias K,, Walker TD,, Goncharova S,, Coyle AJ,, Humbles AA,, Jordana M . 2011. Eosinophils are dispensable for allergic remodeling and immunity in a model of house dust mite-induced airway disease. Am J Respir Crit Care Med 183 : 179188.
158. Lee JJ,, Dimina D,, Macias MP,, Ochkur SI,, McGarry MP,, O’Neill KR,, Protheroe C,, Pero R,, Nguyen T,, Cormier SA,, Lenkiewicz E,, Colbert D,, Rinaldi L,, Ackerman SJ,, Irvin CG,, Lee NA . 2004. Defining a link with asthma in mice congenitally deficient in eosinophils. Science 305 : 17731776.
159. Walsh ER,, Sahu N,, Kearley J,, Benjamin E,, Kang BH,, Humbles A,, August A . 2008. Strain-specific requirement for eosinophils in the recruitment of T cells to the lung during the development of allergic asthma. J Exp Med 205 : 12851292.
160. Nair P,, Pizzichini MM,, Kjarsgaard M,, Inman MD,, Efthimiadis A,, Pizzichini E,, Hargreave FE,, O’Byrne PM . 2009. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 360 : 985993.
161. Prazma CM,, Wenzel S,, Barnes N,, Douglass JA,, Hartley BF,, Ortega H . 2014. Characterisation of an OCS-dependent severe asthma population treated with mepolizumab. Thorax 69 : 11411142.
162. Lukawska JJ,, Livieratos L,, Sawyer BM,, Lee T,, O’Doherty M,, Blower PJ,, Kofi M,, Ballinger JR,, Corrigan CJ,, Gnanasegaran G,, Sharif-Paghaleh E,, Mullen GE . 2014. Real-time differential tracking of human neutrophil and eosinophil migration in vivo . J Allergy Clin Immunol 133 : 233239e231.
163. Teran LM,, Campos MG,, Begishvilli BT,, Schroder JM,, Djukanovic R,, Shute JK,, Church MK,, Holgate ST,, Davies DE . 1997. Identification of neutrophil chemotactic factors in bronchoalveolar lavage fluid of asthmatic patients. Clin Exp Allergy 27 : 396