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214: Type-I interferon controls its own production in immune homeostasis by inducing PPAR-γ expression and an inhibitory PPAR-γ/IRF7 complex

Type-I interferon (IFN) is important for anti-viral immunity, but its over-production is linked to the development of multiple autoimmune diseases. Production of type-I IFN is under the control of the transcription factor IRF7. How type-I IFN signals to attenuate its own production in immune homeost...

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Published in:Cytokine (Philadelphia, Pa.) Pa.), 2013-09, Vol.63 (3), p.293-294
Main Authors: Ripley, Barry, Fujimoto, Minoru, Takemori, Hiroshi, Lee, Soyoung, Han, Yongmei, Yang, Lingli, Ohkawara, Tomoharu, Serada, Satoshi, Chinen, Ichino, Masuda, Kazuya, Kawai, Taro, Naka, Tetsuji, Kishimoto, Tadamitsu
Format: Article
Language:English
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Summary:Type-I interferon (IFN) is important for anti-viral immunity, but its over-production is linked to the development of multiple autoimmune diseases. Production of type-I IFN is under the control of the transcription factor IRF7. How type-I IFN signals to attenuate its own production in immune homeostasis is not known. Here we show that type-I IFN induces expression of PPAR-gamma, which forms an inhibitory interaction with IRF7, attenuating type-I IFN production via the virus-activated (MyD88-independent) pathways in fibroblasts and TLR-activated (MyD88-dependent) pathways in pDCs, and type-I IFN-dependent responses in autoimmunity. Thus all aspects of the type-I IFN system, its production in innate and adaptive immunity and associated immunopathology, are self-controlled through a two-step process of (i) type-I IFN-induced PPAR-gamma expression and (ii) formation of an inhibitory PPAR-gamma/IRF7 complex.
ISSN:1043-4666
1096-0023
DOI:10.1016/j.cyto.2013.06.217