The NLRP3 inflammasome in kidney disease and autoimmunity

The NLRP3 inflammasome is an intracellular platform that converts the proinflammatorycytokines interleukin (IL)-1β and IL-18 to their active forms inresponse to ‘danger’ signals, which can be either host or pathogen derived,and mediates a form of inflammatory cell death called pyroptosis. Thiscomponent of the innate immune system was initially discovered because ofits role in rare autoinflammatory syndromes called cryopyrinopathies, but ithas since been shown to mediate injurious inflammation in a broad range ofdiseases. Inflammasome activation occurs in both immune cells, primarilymacrophages and dendritic cells, and in some intrinsic kidney cells such asthe 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, MCC950and 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.