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The Role and Function of Fcγ Receptors on Myeloid Cells

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  • Authors: Stylianos Bournazos1, Taia T. Wang2, Jeffrey V. Ravetch3
  • Editor: Siamon Gordon4
    Affiliations: 1: Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065; 2: Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065; 3: Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065; 4: Oxford University, Oxford, United Kingdom
  • Source: microbiolspec November 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0045-2016
  • Received 27 July 2016 Accepted 21 September 2016 Published 18 November 2016
  • Jeffrey V. Ravetch, [email protected]
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  • Abstract:

    A key determinant for the survival of organisms is their capacity to recognize and respond efficiently to foreign antigens. This is largely accomplished by the orchestrated activity of the innate and adaptive branches of the immune system. Antibodies are specifically generated in response to foreign antigens, facilitating thereby the specific recognition of antigens of almost infinite diversity. Receptors specific for the Fc domain of antibodies, Fc receptors, are expressed on the surface of the various myeloid leukocyte populations and mediate the binding and recognition of antibodies by innate leukocytes. By directly linking the innate and the adaptive components of immunity, Fc receptors play a central role in host defense and the maintenance of tissue homeostasis through the induction of diverse proinflammatory, anti-inflammatory, and immunomodulatory processes that are initiated upon engagement by the Fc domain. In this chapter, we discuss the mechanisms that regulate Fc domain binding to the various types of Fc receptors and provide an overview of the astonishing diversity of effector functions that are mediated through Fc-FcR interactions on myeloid cells. Lastly, we discuss the impact of FcR-mediated interactions in the context of IgG-mediated inflammation, autoimmunity, susceptibility to infection, and responsiveness to antibody-based therapeutics.

  • Citation: Bournazos S, Wang T, Ravetch J. 2016. The Role and Function of Fcγ Receptors on Myeloid Cells. Microbiol Spectrum 4(6):MCHD-0045-2016. doi:10.1128/microbiolspec.MCHD-0045-2016.


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A key determinant for the survival of organisms is their capacity to recognize and respond efficiently to foreign antigens. This is largely accomplished by the orchestrated activity of the innate and adaptive branches of the immune system. Antibodies are specifically generated in response to foreign antigens, facilitating thereby the specific recognition of antigens of almost infinite diversity. Receptors specific for the Fc domain of antibodies, Fc receptors, are expressed on the surface of the various myeloid leukocyte populations and mediate the binding and recognition of antibodies by innate leukocytes. By directly linking the innate and the adaptive components of immunity, Fc receptors play a central role in host defense and the maintenance of tissue homeostasis through the induction of diverse proinflammatory, anti-inflammatory, and immunomodulatory processes that are initiated upon engagement by the Fc domain. In this chapter, we discuss the mechanisms that regulate Fc domain binding to the various types of Fc receptors and provide an overview of the astonishing diversity of effector functions that are mediated through Fc-FcR interactions on myeloid cells. Lastly, we discuss the impact of FcR-mediated interactions in the context of IgG-mediated inflammation, autoimmunity, susceptibility to infection, and responsiveness to antibody-based therapeutics.

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Structure and composition of the Fc-associated N-linked glycan regulates binding to type I and type II FcγRs. An N-linked glycan structure is attached at the C2 domain of each of the two heavy chains of IgG and consists of a core heptasaccharide structure that is composed of fucose, galactose, -acetylglucosamine, and sialic acid residues. The structure and composition of this Fc-associated glycan determine binding specificity and affinity of the IgG Fc domain for different types of FcγRs. Several glycoform combinations exist with distinct binding capacity to interact with type I and type II FcγRs.

Source: microbiolspec November 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0045-2016
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Overview of type I and type II FcγR structure and expression pattern in myeloid cell populations. Structural characteristics of type I and type II FcγRs. Type I FcγRs belong to the Ig receptor superfamily and are composed of two or three extracellular Ig-like domains that interact with the IgG Fc domain at the hinge-proximal region of the C2 domain. Type II FcγRs comprise DC-SIGN and CD23, both C-type lectin receptors, which bind sialylated Fc IgGs. Expression pattern of type I and type II FcγRs in myeloid leukocyte populations. The expression of several FcγRs is determined by cell differentiation status and is regulated by cytokines like IL-4 and IFN-γ.

Source: microbiolspec November 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0045-2016
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Effector functions and processes that are regulated by Fc-FcγR interactions. Engagement of type I and type II FcγRs by the Fc domain of IgG initiates signaling cascades with diverse proinflammatory, anti-inflammatory, and immunomodulatory consequences on myeloid cells, including granulocytes, monocytes, macrophages, DCs, and platelets. ROS, reactive oxygen species.

Source: microbiolspec November 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.MCHD-0045-2016
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