Epithelial TNF controls cell differentiation and CFTR activity to maintain intestinal mucin homeostasis.

ABSTRACT: The gastrointestinal tract relies on the production, maturation, and transit of mucin to protect against pathogens and to lubricate the epithelial lining. Although the molecular and cellular mechanisms that regulate mucin production and movement are beginning to be understood, the upstream epithelial signals that contribute to mucin regulation remain unclear. Here, we report that the inflammatory cytokine tumor necrosis factor (TNF), generated by the epithelium, contributes to mucin homeostasis by regulating both cell differentiation and cystic fibrosis transmembrane conductance regulator (CFTR) activity. We used genetic mouse models and noninflamed samples from patients with inflammatory bowel disease (IBD) undergoing anti-TNF therapy to assess the effect of in vivo perturbation of TNF. W

SUBMITTER: Reyes EA 

PROVIDER: S-EPMC10575728 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature