The NLRP3 inflammasome in kidney disease and autoimmunity

Research output: Contribution to journalArticleOtherpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)736 - 744
Number of pages9
JournalNephrology
Volume21
Issue number9
DOIs
Publication statusPublished - 2016

Keywords

  • acute kidney injury
  • chronic kidney disease
  • glomerulonephritis
  • inflammasome
  • innate immunity

Cite this

@article{2cb37ee5e68b41fb9a6bdbca459cd71c,
title = "The NLRP3 inflammasome in kidney disease and autoimmunity",
abstract = "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.",
keywords = "acute kidney injury, chronic kidney disease, glomerulonephritis, inflammasome, innate immunity",
author = "Hutton, {Holly Lucinda} and Joshua Ooi and Holdsworth, {Stephen Roger} and Kitching, {Arthur Richard}",
year = "2016",
doi = "10.1111/nep.12785",
language = "English",
volume = "21",
pages = "736 -- 744",
journal = "Nephrology",
issn = "1320-5358",
publisher = "Wiley-Blackwell",
number = "9",

}

The NLRP3 inflammasome in kidney disease and autoimmunity. / Hutton, Holly Lucinda; Ooi, Joshua; Holdsworth, Stephen Roger; Kitching, Arthur Richard.

In: Nephrology, Vol. 21, No. 9, 2016, p. 736 - 744.

Research output: Contribution to journalArticleOtherpeer-review

TY - JOUR

T1 - The NLRP3 inflammasome in kidney disease and autoimmunity

AU - Hutton, Holly Lucinda

AU - Ooi, Joshua

AU - Holdsworth, Stephen Roger

AU - Kitching, Arthur Richard

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - acute kidney injury

KW - chronic kidney disease

KW - glomerulonephritis

KW - inflammasome

KW - innate immunity

UR - http://www.ncbi.nlm.nih.gov/pubmed/27011059

U2 - 10.1111/nep.12785

DO - 10.1111/nep.12785

M3 - Article

VL - 21

SP - 736

EP - 744

JO - Nephrology

JF - Nephrology

SN - 1320-5358

IS - 9

ER -