Article: article from journal or magazin.
Type I interferon inhibits interleukin-1 production and inflammasome activation.
Type I interferon (IFN) is a common therapy for autoimmune and inflammatory disorders, yet the mechanisms of action are largely unknown. Here we showed that type I IFN inhibited interleukin-1 (IL-1) production through two distinct mechanisms. Type I IFN signaling, via the STAT1 transcription factor, repressed the activity of the NLRP1 and NLRP3 inflammasomes, thereby suppressing caspase-1-dependent IL-1β maturation. In addition, type I IFN induced IL-10 in a STAT1-dependent manner; autocrine IL-10 then signaled via STAT3 to reduce the abundance of pro-IL-1α and pro-IL-1β. In vivo, poly(I:C)-induced type I IFN diminished IL-1β production in response to alum and Candida albicans, thus increasing susceptibility to this fungal pathogen. Importantly, monocytes from multiple sclerosis patients undergoing IFN-β treatment produced substantially less IL-1β than monocytes derived from healthy donors. Our findings may thus explain the effectiveness of type I IFN in the treatment of inflammatory diseases but also the observed "weakening" of the immune system after viral infection.
Animals, Apoptosis Regulatory Proteins/physiology, Candida albicans/physiology, Candidiasis/etiology, Candidiasis/immunology, Carrier Proteins/physiology, Caspase 1/deficiency, Caspase 1/genetics, Cells, Cultured/metabolism, Disease Susceptibility, Gene Expression Regulation/drug effects, Humans, Inflammasomes/metabolism, Interferon Inducers/pharmacology, Interferon Type I/biosynthesis, Interferon Type I/genetics, Interferon-beta/therapeutic use, Interleukin-1/biosynthesis, Interleukin-1/genetics, Interleukin-10/physiology, Mice, Mice, Inbred C57BL, Monocytes/immunology, Monocytes/metabolism, Multiple Sclerosis/drug therapy, Multiple Sclerosis/immunology, Peritonitis/etiology, Peritonitis/immunology, Poly I-C/pharmacology, STAT1 Transcription Factor/deficiency, STAT1 Transcription Factor/genetics, STAT3 Transcription Factor/physiology
Web of science
Last modification date