title: IgA, IgA receptors, and their anti-inflammatory properties.
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.
authors.affiliation: Inserm, U1149, Centre de Recherche sur l'Inflammation, Paris, France.
authors.forename: Sanae Ben
authors.initials: SB
authors.lastname: Mkaddem
authors.forename: Ivy
authors.initials: I
authors.lastname: Christou
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Rossato
authors.forename: Laureline
authors.initials: L
authors.lastname: Berthelot
authors.forename: Agnès
authors.initials: A
authors.lastname: Lehuen
authors.forename: Renato C
authors.initials: RC
authors.lastname: Monteiro
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000502:physiology; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry / Q000502:physiology*; D007071:Immunoglobulin A, Secretory / Q000502:physiology; D007249:Inflammation / Q000517:prevention & control*; D037181:Lectins, C-Type / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D011961:Receptors, Fc / Q000737:chemistry / Q000502:physiology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D011961:Receptors, Fc; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C045281:IgA receptor