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Publication : Deubiquitination of NLRP6 inflammasome by Cyld critically regulates intestinal inflammation.

First Author  Mukherjee S Year  2020
Journal  Nat Immunol Volume  21
Issue  6 Pages  626-635
PubMed ID  32424362 Mgi Jnum  J:306372
Mgi Id  MGI:6706628 Doi  10.1038/s41590-020-0681-x
Citation  Mukherjee S, et al. (2020) Deubiquitination of NLRP6 inflammasome by Cyld critically regulates intestinal inflammation. Nat Immunol 21(6):626-635
abstractText  The inflammasome NLRP6 plays a crucial role in regulating inflammation and host defense against microorganisms in the intestine. However, the molecular mechanisms by which NLRP6 function is inhibited to prevent excessive inflammation remain unclear. Here, we demonstrate that the deubiquitinase Cyld prevents excessive interleukin 18 (IL-18) production in the colonic mucosa by deubiquitinating NLRP6. We show that deubiquitination inhibited the NLRP6-ASC inflammasome complex and regulated the maturation of IL-18. Cyld deficiency in mice resulted in elevated levels of active IL-18 and severe colonic inflammation following Citrobacter rodentium infection. Further, in patients with ulcerative colitis, the concentration of active IL-18 was inversely correlated with CYLD expression. Thus, we have identified a novel regulatory mechanism that inhibits the NLRP6-IL-18 pathway in intestinal inflammation.
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