title: The role of inflammasome-derived IL-1 in driving IL-17 responses.
abstract: 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.
authors.affiliation: Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland. kingston.mills@tcd.ie
authors.forename: Kingston H G
authors.initials: KH
authors.lastname: Mills
authors.forename: Lara S
authors.initials: LS
authors.lastname: Dungan
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Jones
authors.forename: James
authors.initials: J
authors.lastname: Harris
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D001419:Bacteria; D001424:Bacterial Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D020169:Caspases / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology; D052638:Particulate Matter / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D058847:Inflammasomes; D007375:Interleukin-1; D020381:Interleukin-17; D020382:Interleukin-18; D052638:Particulate Matter; D020169:Caspases