Abstract:

ABSTRACT   Anti-FcaRI antibody treatment has been reported in recent years to be effective in controlling inflammatory and kidney diseases, such as immune related and nonimmune related renal disease. Inhibitory immunoreceptor tyrosine-based activation motifs (ITAMi) have been found to be involved in the mechanism of treatment other than activating effects, but mechanisms of inhibitory signaling are poorly understood. New evidence of low avidity ligation of the ITAM-associated FcaRI explained how ITAM broadly inhibits heterologous receptors, which involves translocation of  receptor and the associated inhibitory Src homology 2 (SH2) domain–containing phosphatase–1 (SHP-1) to membrane lipid rafts, colocalization of activating receptors with FcaRI and SHP-1 and trafficking to an inhibitory intracellular compartment termed the inhibisome. Thus, ITAM suppressive signals subvert the activating function of rafts to promote incorporation of receptors into supramolecular domains where signaling molecules are deactivated by SHP-1.These results provided new evidence for anti- FcaRI antibody therapy in the treatment of renal disease.

Key words:  immunoreceptors  , FcaRI  , immunoglobulin A   , tyrosine-based motifs