FcγRIII-dependent inhibition of interferon-γ responses mediates suppressive effects of intravenous immune globulin Journal Article
| Authors: | Park-Min, K. H.; Serbina, N. V.; Yang, W.; Ma, X.; Krystal, G.; Neel, B. G.; Nutt, S. L.; Hu, X.; Ivashkiv, L. B. |
| Article Title: | 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 inhibitory effect of IVIG was mediated at least in part by soluble immune complexes and was dependent on FcγRIII but independent of FcγRIIb. These results reveal an unexpected inhibitory role for the activating FcγRIII in mediating suppression of IFN-γ signaling and suggest that inhibition of macrophage responses to IFN-γ contributes to the anti-inflammatory properties of IVIG. © 2007 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; controlled study; human tissue; protein expression; drug efficacy; nonhuman; flow cytometry; protein function; mouse; animal; animals; mice; reverse transcription polymerase chain reaction; gene expression; inflammation; immunoglobulin; in vivo study; drug effect; transfection; gene expression regulation; immunology; disease severity; immune response; genetic transfection; gamma interferon; reverse transcriptase polymerase chain reaction; immunoblotting; fc receptor; receptors, igg; idiopathic thrombocytopenic purpura; antiinflammatory activity; receptor blocking; protein subunit; macrophage; macrophages; autoantibody; molimmuno; listeriosis; listeria monocytogenes; listeria infections; normal human; immunoglobulins, intravenous; macrophage activation; interferon type ii; thrombocytopenic purpura; purpura, thrombocytopenic, idiopathic; gamma interferon receptor |
| Journal Title: | Immunity |
| Volume: | 26 |
| Issue: | 1 |
| ISSN: | 1074-7613 |
| Publisher: | Cell Press |
| Date Published: | 2007-01-01 |
| Start Page: | 67 |
| End Page: | 78 |
| Language: | English |
| DOI: | 10.1016/j.immuni.2006.11.010 |
| PUBMED: | 17239631 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 58" - "Export Date: 17 November 2011" - "CODEN: IUNIE" - "Source: Scopus" |
