The role of inflammasome-derived IL-1 in driving IL-17 responses

Journal of Leukocyte Biology

Kingston H. G. Mills, ¹  Sarah A. Jones  and¹  Lara S. Dungan¹  James Harris ¹ 

[1] Immune Regulation Research Group and  Immunology Research Centre, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland

关键词: Th17 cell;    γδ T cell;    IL-18;    caspase-1;    autoimmunity;    infection;   

DOI  :  10.1189/jlb.1012543

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

NLRs are members of the PRR family that sense microbial pathogens and mediate host innate immune responses to infection. Certain NLRs can assemble into a multiprotein complex called the inflammasome, which activates casapse-1 required for the cleavage of immature forms of IL-1β and IL-18 into active, mature cytokines. The inflammasome is activated by conserved, exogenous molecules from microbes and nonmicrobial molecules, such as asbestos, alum, or silica, as well as by endogenous danger signals, such as ATP, amyloid-β, and sodium urate crystals. Activation of the inflammasome is a critical event triggering IL-1-driven inflammation and is central to the pathology of autoinflammatory diseases, such as gout and MWS. Recent studies have also shown IL-1 or IL-18, in synergy with IL-23, can promote IL-17-prduction from Th17 cells and γδ T cells, and this process can be regulated by autophagy. IL-1-driven IL-17 production plays a critical role in host protective immunity to infection with fungi, bacteria, and certain viruses. However, Th17 cells and IL-17-seceting γδ T cells, activated by inflammasome-derived IL-1 or IL-18, have major pathogenic roles in many autoimmune diseases. Consequently, inflammasomes are now major drug targets for many autoimmune and chronic inflammatory diseases, as well as autoinflammatory diseases.

【 授权许可】

Unknown