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IgA, IgA Receptors, and Their Anti-inflammatory Properties

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Fc Receptors

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 382))

Abstract

Immunoglobulin A (IgA) is the most abundantly produced antibody isotype in mammals. The primary function of IgA is to maintain homeostasis at mucosal surfaces and play a role in immune protection. IgA functions mainly through interaction with multiple receptors including IgA Fc receptor I (FcαRI), transferrin receptor 1 (CD71), asialoglycoprotein receptor (ASGPR), Fcα/μR, FcRL4, and DC-SIGN/SIGNR1. In this review we discuss recent data demonstrating anti-inflammatory functions of IgA through two receptors, the FcαRI and DC-SIGN/SIGNR1 interactions in the regulation of immunity. Serum monomeric IgA is able to mediate an inhibitory signal following the interaction with FcαRI. It results in partial phosphorylation of its FcRγ-ITAM and the recruitment of the tyrosine phosphatase SHP-1, which induces cell inhibition following the formation of intracellular clusters named inhibisomes. In contrast, cross-linking of FcαRI by multimeric ligands induces a full phosphorylation of the FcRγ-ITAM leading to the recruitment of the tyrosine kinase Syk and cell activation. In addition, secretory IgA can mediate a potent anti-inflammatory function following the sugar-dependent interaction with SIGNR1 on dendritic cells which induces an immune tolerance via regulatory T cell expansion. Overall, the anti-inflammatory effect of serum and secretory IgA plays a crucial role in the physiology and in the prevention of tissue damage in multiple autoimmune and inflammatory diseases.

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Acknowledgments

This work was supported in part by grants from Agence Nationale de la Recherche (ANR grants MIEN-2009 and BLANC International-2012) and from the LabEx Inflamex. S.B.M. was supported by a grant from the French Foundation ARC (PDF20100601037).

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Authors and Affiliations

  1. Inserm, U1149, Centre de Recherche sur l’Inflammation, Paris, France

    Sanae Ben Mkaddem, Ivy Christou, Elisabetta Rossato, Laureline Berthelot & Renato C. Monteiro

  2. CNRS ERL8252, Paris, France

    Sanae Ben Mkaddem, Ivy Christou, Elisabetta Rossato, Laureline Berthelot & Renato C. Monteiro

  3. Université Paris Diderot, Sorbonne Paris Cité, Site Xavier Bichat, Paris, France

    Sanae Ben Mkaddem, Ivy Christou, Elisabetta Rossato, Laureline Berthelot & Renato C. Monteiro

  4. Laboratoire d’Excellence Inflamex, Paris, France

    Sanae Ben Mkaddem, Ivy Christou, Elisabetta Rossato, Laureline Berthelot, Agnès Lehuen & Renato C. Monteiro

  5. Inserm, U1016, Institut Cochin, Paris, France

    Agnès Lehuen

  6. Laboratoire Dysfonctionnements Immunitaires, DHU Fire, Hôpital Bichat Claude Bernard, Paris, France

    Renato C. Monteiro

  7. INSERM UMR1149 & CNRS ERL8252, Faculté de Médecine Xavier Bichat, 16 Rue Henri Huchard, Paris, 75018, Cedex 18, France

    Renato C. Monteiro

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  1. Sanae Ben Mkaddem
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  2. Ivy Christou
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  3. Elisabetta Rossato
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  4. Laureline Berthelot
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  5. Agnès Lehuen
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  6. Renato C. Monteiro
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Correspondence to Renato C. Monteiro .

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  1. Institut Pasteur, Paris, France

    Marc Daeron

  2. Department of Biology, Institute of Genetics, University of Erlangen-Nürnberg, Erlangen, Germany

    Falk Nimmerjahn

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Mkaddem, S.B., Christou, I., Rossato, E., Berthelot, L., Lehuen, A., Monteiro, R.C. (2014). IgA, IgA Receptors, and Their Anti-inflammatory Properties. In: Daeron, M., Nimmerjahn, F. (eds) Fc Receptors. Current Topics in Microbiology and Immunology, vol 382. Springer, Cham. https://doi.org/10.1007/978-3-319-07911-0_10

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