Paneth cell SIRT1 deficiency increases intestinal stress resistance by modulating the gut microbiota

ABSTRACT: 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 remain unclear. Here, we report that SIRT1, the most conserved mammalian NAD+-dependent protein deacetylase and a well-known genetic repressor of inflammation, cell-autonomously suppresses Paneth cell function and sensitizes the gut epithelium to environmental stress. Specifically, deletion of Paneth cell SIRT1 in mice elevates Wnt signaling and ATF4/endoplasmic reticulum stress pathway in Paneth cells. These molecular alterations are coupled w

SUBMITTER: Liz, M Garcia-Peterson 

PROVIDER: S-SCDT-10_1038-S44319-026-00726-3 | biostudies-other |

REPOSITORIES: biostudies-other