Gut epithelial TSC1/mTOR controls RIPK3-dependent necroptosis in intestinal inflammation and cancer.

ABSTRACT: Although Western diet and dysbiosis are the most prominent environmental factors associated with inflammatory bowel diseases (IBDs), the corresponding host factors and cellular mechanisms remain poorly defined. Here we report that the TSC1/mTOR pathway in the gut epithelium represents a metabolic and innate immune checkpoint for intestinal dysfunction and inflammation. mTOR hyperactivation triggered by Western diet or Tsc1 ablation led to epithelium necroptosis, barrier disruption, and predisposition to dextran sulfate sodium-induced colitis and inflammation-associated colon cancer. Mechanistically, our results uncovered a critical role for TSC1/mTOR in restraining the expression and activation of RIPK3 in the gut epithelium through TRIM11-mediated ubiquitination and autophagy-dependent de

SUBMITTER: Xie Y 

PROVIDER: S-EPMC7108921 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature