ABSTRACT The receptors for the Fc of immunoglobulin (FcRs) link humoral and cellular immune reactions and have important regulatory functions. Three classes of human FcγR (FcγRI/CD64, FcγRII/CD32, and FcγRIII/CD16) are present as activation (FcγRI, FcγRIIA and FcIIA) and inhibitory (FcγRIIB) pairs in immune networks. Stimulatory FcγR transduces the signals through the immune-receptor tyrosine-based activation motif (ITAM); inhibitory FcgRIIB transduces through tyrosine-based inhibitory motif (ITIM). Regulation of cellular signaling and clearance of ICs linked to antigen presentation are the physiological roles of FcRs. Coligation between FcgRIIB and FceRI relay the tyrosine phosphorylation in the ITIM of FcgRIIB by Lyn to inhibitory signal thereafter. Hypersensitivity responses by FcRs were advanced by in vivo observations in FcR-deficient mice. Genetic polymorphism in FcRs have been described in patients with autoimmune diseases The modulation of active or inhibitory signaling including IVIG, hyposensitization and mAb immunotherapy, are promising strategies for treating the inflammatory diseases.
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