title: The NLRP3 inflammasome in kidney disease and autoimmunity.
abstract: The NLRP3 inflammasome is an intracellular platform that converts the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 to their active forms in response to 'danger' signals, which can be either host or pathogen derived, and mediates a form of inflammatory cell death called pyroptosis. This component of the innate immune system was initially discovered because of its role in rare autoinflammatory syndromes called cryopyrinopathies, but it has since been shown to mediate injurious inflammation in a broad range of diseases. Inflammasome activation occurs in both immune cells, primarily macrophages and dendritic cells, and in some intrinsic kidney cells such as the renal tubular epithelium. The NLRP3 inflammasome has been implicated in the pathogenesis of a number of renal conditions, including acute kidney injury, chronic kidney disease, diabetic nephropathy and crystal-related nephropathy. The inflammasome also plays a role in autoimmune kidney disease, as IL-1β and IL-18 influence adaptive immunity through modulation of T helper cell subsets, skewing development in favour of Th17 and Th1 cells that are important in the development of autoimmunity. Both IL-1 blockade and two recently identified specific NLRP3 inflammasome blockers, MCC950 and β-hydroxybutyrate, have shown promise in the treatment of inflammasome-mediated conditions. These targeted therapies have the potential to be of benefit in the growing number of kidney diseases in which the NLRP3 inflammasome has been implicated.
authors.affiliation: Centre for Inflammatory Diseases, Department of Medicine, Monash University, Melbourne, Victoria, Australia.|Department of Nephrology, Monash Health, Melbourne, Victoria, Australia.
authors.forename: Holly L
authors.initials: HL
authors.lastname: Hutton
authors.affiliation: Centre for Inflammatory Diseases, Department of Medicine, Monash University, Melbourne, Victoria, Australia.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Ooi
authors.affiliation: Centre for Inflammatory Diseases, Department of Medicine, Monash University, Melbourne, Victoria, Australia.|Department of Nephrology, Monash Health, Melbourne, Victoria, Australia.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Holdsworth
authors.affiliation: Centre for Inflammatory Diseases, Department of Medicine, Monash University, Melbourne, Victoria, Australia.|Department of Nephrology, Monash Health, Melbourne, Victoria, Australia.|Department of Paediatric Nephrology, Monash Health, Melbourne, Victoria, Australia.
authors.forename: A Richard
authors.initials: AR
authors.lastname: Kitching
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D015551:Autoimmunity; D006801:Humans; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D020382:Interleukin-18 / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D007668:Kidney / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D058847:Inflammasomes; D018836:Inflammation Mediators; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
keywords: acute kidney injury; chronic kidney disease; glomerulonephritis; inflammasome; innate immunity