The human immunoglobulin A Fc receptor FcαRI: a multifaceted regulator of mucosal immunity

Abstract

Immunoglobulin A (IgA) is commonly recognized as the most prevalent antibody (Ab) at mucosal sites with an important role in defense by shielding mucosal surfaces from invasion by pathogens. However, its potential to both actively dampen excessive immune responses or to initiate potent proinflammatory cellular processes is less well known. Interestingly, either functional outcome is mediated through interaction with the myeloid IgA Fc receptor FcαRI (CD89). Monomeric interaction of IgA with FcαRI triggers inhibitory signals that block activation via other receptors, whereas multimeric FcαRI crosslinking induces phagocytosis, reactive oxygen species production, antigen presentation, Ab-dependent cellular cytotoxicity, and cytokine release. Thus, FcαRI acts as a regulator between anti- and proinflammatory responses of IgA. As such, the biology of FcαRI, and its multifaceted role in immunity will be the focus of this review.

Re-thinking the functions of IgA+plasma cells

“…In addition, IgA has been shown to facilitate the uptake of luminal Ag across the intestinal epithelium, enhancing Ag-presentation and priming of Ag-specific immunity. 8,9,[80][81][82] Since the gut is a complex system with 3 main interacting components, the intestinal epithelium, the microbiota and the immune system, alterations in IgA production leads to changes in the composition of the intestinal microbiota and altered intestinal barrier function. Mucosal IgA has been shown to play an important role in containing potentially invasive commensal bacteria, suggesting that IgA exerts protective effects at the level of barrier function in the gut.…”

Human IgA Fc Receptor FcαRI (CD89) Triggers Different Forms of Neutrophil Death Depending on the Inflammatory Microenvironment

“…Human neutrophils express FcaRI (CD89), the most prominent receptor for IgA, which binds IgA by two extracellular binding sites (16,17). IgA represents the most dominant Ab isotype in mucosal tissues and the second most prevalent Ab in the blood; altogether, it accounts for about three quarters of the body's total Ab production (18).…”

IgA Enhances NETosis and Release of Neutrophil Extracellular Traps by Polymorphonuclear Cells via Fcα Receptor I

“…Cross-linking of FcaRI induces a multitude of proinflammatory functions that include phagocytosis, respiratory burst, degranulation, Ab-dependent cellular cytotoxicity, Ag presentation, and release of cytokines and inflammatory mediators (4,8). Few FcaRI-positive cells are observed in mucosal areas in homeostatic conditions (9).…”

“…FcaRI is a member of the Fc receptor Ig superfamily that also includes Fc receptors for IgG and IgE, and is exclusively expressed on myeloid cells, including neutrophils, eosinophils, monocytes, and Kupffer cells (4)(5)(6)(7). Cross-linking of FcaRI induces a multitude of proinflammatory functions that include phagocytosis, respiratory burst, degranulation, Ab-dependent cellular cytotoxicity, Ag presentation, and release of cytokines and inflammatory mediators (4,8).…”