FcgammaRIII-dependent inhibition of interferon-gamma responses mediates suppressive effects of intravenous immune globulin.

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Park-Min KH, Serbina NV, Yang W, Ma X, Krystal G, Neel BG, Nutt SL, Hu X, Ivashkiv LB

FcgammaRIII-dependent inhibition of interferon-gamma responses mediates suppressive effects of intravenous immune globulin.

Immunity. 2007 Jan;26(1):67-78.

PubMed ID

17239631 [ View in PubMed

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Abstract

Intravenous immune globulin (IVIG) suppresses autoantibody-mediated inflammation by inducing and activating the inhibitory Fc receptor FcgammaRIIb and downstream negative signaling pathways. We investigated the effects of IVIG on cellular responses to interferon-gamma (IFN-gamma), a potent macrophage activator that exacerbates inflammation. Our study showed that IVIG blocked IFN-gamma signaling and IFN-gamma-induced gene expression and suppressed IFN-gamma function in vivo during immune responses to Listeria monocytogenes and in an IFN-gamma-enhanced model of immune thrombocytopenic purpura. The mechanism of inhibition of IFN-gamma signaling was suppression of expression of the IFNGR2 subunit of the IFN-gamma receptor. The inhibitory effect of IVIG was mediated at least in part by soluble immune complexes and was dependent on FcgammaRIII but independent of FcgammaRIIb. These results reveal an unexpected inhibitory role for the activating FcgammaRIII in mediating suppression of IFN-gamma signaling and suggest that inhibition of macrophage responses to IFN-gamma contributes to the anti-inflammatory properties of IVIG.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Interferon gamma-1b	Interferon gamma receptor 2	Protein	Humans	Yes	Binder	Details