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IgG and Fcγ Receptors in Intestinal Immunity and Inflammation

2019; Frontiers Media; Volume: 10; Linguagem: Inglês

10.3389/fimmu.2019.00805

1664-3224

Tomas Castro‐Dopico, Menna R. Clatworthy,

Immune Cell Function and Interaction

Fcγ receptors (FcγR) are cell surface glycoproteins that mediate cellular effector functions of immunoglobulin G (IgG) antibodies. Genetic variation in FcγR genes can influence susceptibility to a variety of antibody-mediated autoimmune and inflammatory disorders, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). More recently, however, genetic studies have implicated altered FcγR signalling in the pathogenesis of inflammatory bowel disease (IBD), a condition classically associated with dysregulated innate and T cell immunity. Specifically, a variant of the activating receptor, FcγRIIA, with low affinity for IgG, confers protection against the development of ulcerative colitis, a subset of IBD, leading to a re-evaluation of the role of IgG and FcγRs in gastrointestinal tract immunity, an organ system traditionally associated with IgA. In this review, we summarise our current understanding of IgG and FcγR function at this unique host-environment interface, from the pathogenesis of colitis and defence against enteropathogens, its contribution to maternal-foetal cross-talk and susceptibility to cancer. Finally, we discuss the therapeutic implications of this information, both in terms of how FcγR signalling pathways may be targeted for the treatment of IBD and how FcγR engagement may influence the efficacy of therapeutic monoclonal antibodies in IBD.