A genetically determined molecular switch modulates the anti-inflammatory potential of human IgA.

ABSTRACT: Fc receptor-driven immune system activity typically reflects a balance of activating and inhibitory mechanisms, mediated by the immunoreceptor tyrosine-based activation motif (ITAM) or inhibition motif (ITIM) in the ligand-binding alpha chain (FcγRIIa - c) or the canonical ITAM in the associated Fc receptor γ-chain (FcRγ). A second role for the ITAM, an inhibitory role known as ITAM_i, was initially recognized for the FcαRI-FcRγ signaling pair. We report an FcRγ-independent mechanism for inhibitory signaling by the IgA-binding receptor, FcαRI (CD89) in which the natural Ser²⁴⁸Gly variant in the cytoplasmic domain of the FcαRI α-chain alters the signaling capacity of FcαRI and constitutes a serine-based genetically determined switch for regulation of the anti- and proin

SUBMITTER: Gibson AW 

PROVIDER: S-EPMC12420274 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature