Epithelial TNF Receptor Signaling Promotes Mucosal Repair in Inflammatory Bowel Disease.

ABSTRACT: TNF plays an integral role in inflammatory bowel disease (IBD), as evidenced by the dramatic therapeutic responses in Crohn's disease (CD) patients induced by chimeric anti-TNF mAbs. However, treatment of CD patients with etanercept, a decoy receptor that binds soluble TNF, fails to improve disease. To explore this discrepancy, we investigated the role of TNF signaling in Wnt/β-catenin-mediated intestinal stem cell and progenitor cell expansion in CD patients, human cells, and preclinical mouse models. We hypothesized that TNF exerts beneficial effects on intestinal epithelial cell (IEC) responses to injury. In CD patients, intestinal stem cell and progenitor cell Wnt/β-catenin signaling correlates with inflammation status. TNF-deficient (Tnf^-/-) mice exhibited increased

SUBMITTER: Bradford EM 

PROVIDER: S-EPMC5568528 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature