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Cited by 431

The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.

NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis

Open access
Hirota, Simon A., Ng, Jeffrey, Lueng, Alan, Khajah, Maitham, Parhar, Ken, Li, Yan, Lam, Victor, Potentier, Mireille S., Ng, Kelvin, Bawa, Misha, McCafferty, Donna-Marie, Rioux, Kevin P., Ghosh, Subrata, Xavier, Ramnik J., Colgan, Sean P., Tschopp, Jurg, Muruve, Daniel, MacDonald, Justin A., Beck, Paul L.·2011·Inflammatory Bowel Diseases

Abstract

BACKGROUND: Attenuated innate immune responses to the intestinal microbiota have been linked to the pathogenesis of Crohn's disease (CD). Recent genetic studies have revealed that hypofunctional mutations of NLRP3, a member of the NOD-like receptor (NLR) superfamily, are associated with an increased risk of developing CD. NLRP3 is a key component of the inflammasome, an intracellular danger sensor of the innate immune system. When activated, the inflammasome triggers caspase-1-dependent processing of inflammatory mediators, such as IL-1β and IL-18. METHODS: In the current study we sought to assess the role of the NLRP3 inflammasome in the maintenance of intestinal homeostasis through its regulation of innate protective processes. To investigate this role, Nlrp3(-/-) and wildtype mice were assessed in the dextran sulfate sodium and 2,4,6-trinitrobenzenesulfonic acid models of experimental colitis. RESULTS: Nlrp3(-/-) mice were found to be more susceptible to experimental colitis, an observation that was associated with reduced IL-1β, reduced antiinflammatory cytokine IL-10, and reduced protective growth factor TGF-β. Macrophages isolated from Nlrp3(-/-) mice failed to respond to bacterial muramyl dipeptide. Furthermore, Nlrp3-deficient neutrophils exhibited reduced chemotaxis and enhanced spontaneous apoptosis, but no change in oxidative burst. Lastly, Nlrp3(-/-) mice displayed altered colonic β-defensin expression, reduced colonic antimicrobial secretions, and a unique intestinal microbiota. CONCLUSIONS: Our data confirm an essential role for the NLRP3 inflammasome in the regulation of intestinal homeostasis and provide biological insight into disease mechanisms associated with increased risk of CD in individuals with NLRP3 mutations.

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Metadata

Authors
Hirota, S. A., Ng, J., Lueng, A., Khajah, M., Parhar, K., Li, Y., Lam, V., Potentier, M. S., Ng, K., Bawa, M., McCafferty, D.-M., Rioux, K. P., Ghosh, S., Xavier, R. J., Colgan, S. P., Tschopp, J., Muruve, D., MacDonald, J. A., & Beck, P. L.
Venue
Inflammatory Bowel Diseases
Published
2011-06
Volume
17
Issue
6
Pages
1359-1372
ISSN
1078-0998 (ISSN-L)
OpenAlex
W2142145460
Cited by
431
References
12
FWCI
9.22
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis. https://app.cochat.ai/papers/10.1002/ibd.21478
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Hirota, S. A., Ng, J., Lueng, A., Khajah, M., Parhar, K., Li, Y., Lam, V., Potentier, M. S., Ng, K., Bawa, M., McCafferty, D.-M., Rioux, K. P., Ghosh, S., Xavier, R. J., Colgan, S. P., Tschopp, J., Muruve, D., MacDonald, J. A., & Beck, P. L. (2011). NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis. Inflammatory Bowel Diseases. https://doi.org/10.1002/ibd.21478

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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