title: Anti-inflammatory role of the IgA Fc receptor (CD89): from autoimmunity to therapeutic perspectives.
abstract: The human immunoglobulin A (IgA) plays a key role in immune protection. IgA is the second most prevalent antibody in the serum. IgA-deficient patients frequently develop autoimmune or inflammatory diseases. The IgA function is mainly mediated through its interaction with the myeloid IgA Fc receptor FcαRI (CD89). FcαRI, an immunoreceptor tyrosine-based activation motif (ITAM)-bearing receptor, has a dual function in immunity. Monovalent targeting of FcαRI, by anti-FcαRI Fab or monomeric IgA, triggers potent inhibitory ITAM (ITAMi) signaling through the associated FcRγ chain. This results in a low-intensity signaling cascade promoting recruitment of the tyrosine phosphatase SHP-1, which induces cell inhibition of multiple types of activation signals. In contrast, cross-linking of FcαRI by multimeric ligand induces a high-intensity signaling pathway that leads to the recruitment of the tyrosine kinase Syk and to cell activation. Thus, FcαRI acts as a regulator, which mediates both anti- and pro-inflammatory functions of IgA depending on the type of interaction. This balance is of great importance to prevent tissue damage in immunopathology and to ensure the return of activated cells to a resting state. The role of the IgA-FcαRI interaction in the activation of different signaling pathways and its multifaceted role in immunity are discussed.
authors.affiliation: Inserm U699, Paris, France.
authors.forename: Sanae
authors.initials: S
authors.lastname: Ben Mkaddem
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Rossato
authors.forename: Nicholas
authors.initials: N
authors.lastname: Heming
authors.forename: Renato C
authors.initials: RC
authors.lastname: Monteiro
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology*
chemical_list: D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc