Fc gamma RIII-dependent inhibition of interferon-gamma responses mediates suppressive effects of intravenous immune globulin
- Author(s)
- Park-Min, KH; Serbina, NV; Yang, WT; Ma, XJ; Krystal, G; Neel, BG; Nutt, SL; Hu, XY; Ivashkiv, LB;
- Details
- Publication Year 2007-01,Volume 26,Issue #1,Page 67-78
- Journal Title
- IMMUNITY
- Publication Type
- Journal Article
- Abstract
- Intravenous immune globulin (IVIG) suppresses autoantibody-mediated inflammation by inducing and activating the inhibitory Fc receptor Fc gamma RIIb 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 Fc gamma RIII but independent of Fc gamma RIIb. These results reveal an unexpected inhibitory role for the activating Fc gamma RIII 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.
- Publisher
- CELL PRESS
- Keywords
- AUTOIMMUNE-DISEASE; IFN-GAMMA; INFLAMMATORY MYOPATHIES; LISTERIA-MONOCYTOGENES; KAWASAKI-DISEASE; RECEPTOR; IMMUNOGLOBULIN; EXPRESSION; COMPLEXES; IGG
- Publisher's Version
- https://doi.org/10.1016/j.immuni.2006.11.010
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2007-01-01 12:00:00