FcγRIII-Dependent Inhibition of Interferon-γ Responses Mediates Suppressive Effects of Intravenous Immune Globulin

Abstract

Intravenous immune globulin (IVIG) suppresses autoantibody-mediated inflammation by inducing and activating the inhibitory Fc receptor FcγRIIb and downstream negative signaling pathways. We investigated the effects of IVIG on cellular responses to interferon-γ (IFN-γ), a potent macrophage activator that exacerbates inflammation. Our study showed that IVIG blocked IFN-γ signaling and IFN-γ-induced gene expression and suppressed IFN-γ function in vivo during immune responses to Listeria monocytogenes and in an IFN-γ-enhanced model of immune thrombocytopenic purpura. The mechanism of inhibition of IFN-γ signaling was suppression of expression of the IFNGR2 subunit of the IFN-γ receptor. The inh..