Journal
IMMUNITY
Volume 32, Issue 3, Pages 379-391Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2010.03.003
Keywords
-
Categories
Funding
- Fonds voor Wetenschappelijk Onderzoek-Vlaanderen
- National Institutes of Health [AR056296]
- Cancer Center Support Grant (CCSG) [2 P30 CA 21765]
- American Lebanese Syrian Associated Charities (ALSAC)
Ask authors/readers for more resources
Decreased expression of the Nlrp3 protein is associated with susceptibility to Crohn's disease. However, the role of Nlrp3 in colitis has not been characterized. Nlrp3 interacts with the adaptor protein ASC to activate caspase-1 in inflammasomes, which are protein complexes responsible for the maturation and secretion of interleukin-1 beta (IL-1 beta) and IL-18. Here, we showed that mice deficient for Nlrp3 or ASC and caspase-1 were highly susceptible to dextran sodium sulfate (DSS)-induced colitis. Defective inflammasome activation led to loss of epithelial integrity, resulting in systemic dispersion of commensal bacteria, massive leukocyte infiltration, and increased chemokine production in the colon. This process was a consequence of a decrease in IL-18 in mice lacking components of the Nlrp3 inflammasome, resulting in higher mortality rates. Thus, the NIrp3 inflammasome is critically involved in the maintenance of intestinal homeostasis and protection against colitis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available