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 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.