Fc fragment of IgA receptor I (FcαRI)

Fc fragment of IgA receptor I (FcαRI), also known as CD89, is a transmembrane receptor that specifically binds to the heavy-chain constant region of Immunoglobulin A (IgA) antibodies[1]. The receptor is encoded by the FCAR gene located on chromosome 19 at 19q13.4 within the leukocyte receptor complex, which distinguishes it from other Fc receptors that are typically encoded on chromosome 1[1][2]. FcαRI is expressed on the cell surface of myeloid lineage cells, including neutrophils, monocytes, macrophages, eosinophils, Kupffer cells, and certain dendritic cell subsets[1][3]. Notably, it is absent from intestinal macrophages and does not appear on mast cells[1]. The receptor consists of two extracellular immunoglobulin-like domains (EC1 and EC2) positioned at approximately a 90-degree angle to each other, a transmembrane domain, and a short intracellular domain[1][9]. The receptor cannot perform signaling independently and requires association with a dimeric form of the FcR gamma-chain, which contains immunoreceptor tyrosine-based activation motifs (ITAMs) responsible for relaying signals into the cell[1][3]. The molecular weight of FcαRI varies between 55-75 kDa on neutrophils and monocytes, and 70-100 kDa on eosinophils due to extensive N-linked and O-linked glycosylation[3][9]. FcαRI exhibits unique dual functionality depending on the state of bound IgA. When multiple IgA molecules in immune complexes bind and cross-link FcαRI, it triggers pro-inflammatory responses including phagocytosis, cytokine release, respiratory bursts, antibody-dependent cell-mediated cytotoxicity, and production of reactive oxygen species[1][3]. Conversely, when monomeric serum IgA binds FcαRI monovalently without cross-linking, it initiates inhibitory ITAM (ITAMi) signaling that produces anti-inflammatory responses and dampens activation by other Fc receptors such as FcγR and FcεRI[1][3]. This inhibitory mechanism supports immune homeostasis in the absence of pathogens. The receptor requires priming through inside-out signaling before it can bind IgA with increased affinity. This priming occurs when cytokines signaling infection activate PI3K, p38, and PKC pathways, leading to dephosphorylation of the Serine 263 residue on the FcαRI intracellular domain[1]. Two FcαRI allelic variants exist, differing at position 248 (serine or glycine), with the glycine variant showing enhanced ability to signal for IL-6 release[1]. FcαRI plays significant roles in maintaining appropriate immune responses in both systemic and mucosal compartments and has been identified as a potential molecular target for treating autoimmune conditions such as lupus and glomerulonephritis[12][13].

Other names

CD89Cluster of Differentiation 89FCAR (gene name)IgA receptorFc alpha receptor type I

The search results indicate FcαRI is being investigated as a molecular target for treatment, particularly for lupus, but specific therapeutic mechanisms are not detailed in the provided sources.