Fc fragment of IgA receptor (FcαRI (also known as CD89))

The Fc fragment of IgA receptor (FcαRI, also known as CD89) is a cell surface glycoprotein primarily expressed on myeloid lineage cells such as neutrophils, monocytes/macrophages, eosinophils, and some dendritic cells. It is the principal human receptor for immunoglobulin A (IgA), especially important at mucosal surfaces where it mediates first-line defense against pathogens by facilitating immune exclusion—trapping antigens/pathogens in mucus—and promoting their clearance through phagocytosis or ADCC. Upon cross-linking by multivalent IgA immune complexes, FcαRI associates with the common gamma chain containing an immunoreceptor tyrosine-based activation motif (ITAM), initiating intracellular signaling cascades involving kinases like Fyn/Lyn and Syk. This results in pro-inflammatory responses including cytokine release and enhanced microbicidal activity. Alternatively, monomeric engagement can trigger inhibitory signals via ITAMi mechanisms to limit excessive inflammation. Dysregulation or overactivation of this pathway has been implicated in autoimmune conditions such as rheumatoid arthritis—where high levels of pathogenic IgA autoantibodies drive joint inflammation—and is being explored therapeutically for cancer immunotherapy using engineered antibodies that recruit myeloid effector cells via FcαRI[1][2][4].

Other names

CD89Fc alpha receptorIgA Fc receptorFCAR

Engagement by IgA immune complexes leads to cross-linking of the receptor, triggering ITAM-mediated signaling cascades that activate effector functions such as phagocytosis, ADCC, cytokine production, and respiratory burst[1][2][4]. Monomeric binding can induce inhibitory signaling via ITAMi pathways to dampen inflammation[1].