The NLRP3 inflammasome in kidney disease and autoimmunity

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 c...

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Bibliographic Details
Published in:Nephrology (Carlton, Vic.) Vic.), 2016-09, Vol.21 (9), p.736-744
Main Authors: Hutton, Holly L, Ooi, Joshua D, Holdsworth, Stephen R, Kitching, A Richard
Format: Article
Language:English
Subjects:
acute kidney injury
Animals
Autoimmune Diseases - immunology
Autoimmune Diseases - metabolism
Autoimmune Diseases - pathology
Autoimmune Diseases - therapy
Autoimmunity
chronic kidney disease
glomerulonephritis
Humans
inflammasome
Inflammasomes - immunology
Inflammasomes - metabolism
Inflammation Mediators - immunology
Inflammation Mediators - metabolism
innate immunity
Interleukin-18 - immunology
Interleukin-18 - metabolism
Interleukin-1beta - immunology
Interleukin-1beta - metabolism
Kidney - immunology
Kidney - metabolism
Kidney - pathology
Kidney Diseases - immunology
Kidney Diseases - metabolism
Kidney Diseases - pathology
Kidney Diseases - therapy
NLR Family, Pyrin Domain-Containing 3 Protein - immunology
NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
Signal Transduction
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Summary: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. Summary at a Glance Recent studies in animal models and cell culture suggest a broad role for NLRP3 inflammasome activation in renal disease. Hutton et al provide a timely review of the latest animal and human data in this important area, and discuss therapeutic opportunities afforded by targeting the inflammasome.
ISSN:1320-5358
1440-1797
DOI:10.1111/nep.12785