Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41467-017-01917-2
Keywords
-
Categories
Funding
- National Key Basic Research Programs [2015CB554302, 2014CB541905]
- Natural Science Foundation of China [91429307, 31370892, 31570895, 31330005, 81401141, 81761128012]
- Strategic Priority Research Program [XDPB0303]
- International Partnership Program of the Chinese Academy of Sciences [153831KYSB20160009]
- Science and Technology Commission of Shanghai Municipality [14YF1402200]
Ask authors/readers for more resources
Inflammasomes are involved in gut homeostasis and inflammatory pathologies, but the role of NLRP3 inflammasome in these processes is not well understood. Cryopyrin-associated periodic syndrome (CAPS) patients with NLRP3 mutations have autoinflammation in skin, joints, and eyes, but not in the intestine. Here we show that the intestines of CAPS model mice carrying an Nlrp3(R258W) mutation maintain homeostasis in the gut. Additionally, such mice are strongly resistant to experimental colitis and colorectal cancer; this is mainly through a remodelled gut microbiota with enhanced anti-inflammatory capacity due to increased induction of regulatory T cells (T-regs). Mechanistically, NLRP3(R258W) functions exclusively in the lamina propria mononuclear phagocytes to directly enhance IL-1 beta but not IL-18 secretion. Increased IL-1 beta boosts local antimicrobial peptides to facilitate microbiota remodelling. Our data show that NLRP3(R258W)-induced remodelling of the gut microbiota, induces local T-regs to maintain homeostasis and compensate for otherwise-detrimental intestinal inflammation.
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