Paneth cell SIRT1 deficiency protects against DSS-induced colitis
Paneth cells, intestine-originated innate immune-like cells, are important for maintenance of the intestinal stem cell niche, gut microbiota, and gastrointestinal barrier.  Dysfunctional Paneth cells under pathological conditions are a site of origin for intestinal inflammation. However, mechanisms underlying stress-induced Paneth cell dysregulation remains unclear. We have previously reported that deletion of SIRT1 in the intestinal epithelium (SIRT1 iKO) leads to hyperaction of Paneth cells along with an increased sensitivity to Dextran sodium sulfate (DSS)-induced colitis. We recently generated a Paneth-cell specific SIRT1 KO mouse model (SIRT1 PKO). Similar to mice with SIRT1 iKO mice, SIRT1 PKO mice had increased abundance as well as hyperactivation of Paneth cells in vivo and in cultured intestinal organoids. However, in contrast to the hypersensitivity of SIRT1 iKO mice to chemical- or age-induced inflammation, SIRT1 PKO mice were protected from Dextran sodium sulfate (DSS)-colitis. Overall design: Nine-month old Flox control and SIRT1 PKO female mice were challenged with a chronic colitis model by feeding mice with two cycles of 7-day 2.5% DSS drinking water separated by a 14-day regular water break. Body weights and rectal bleeding were monitored daily during the DSS treatment and one week immediately after DSS treatment. According to the animal protocol, mice with more than 20% loss of their initial body mass were sacrificed during the experiments.