Direct signaling of TL1A-DR3 on fibroblasts induces intestinal fibrosis in vivo.

ABSTRACT: Tumor necrosis factor-like cytokine 1A (TL1A, TNFSF15) is implicated in inflammatory bowel disease, modulating the location and severity of inflammation and fibrosis. TL1A expression is increased in inflamed mucosa and associated with fibrostenosing Crohn's disease. Tl1a-overexpression in mice causes spontaneous ileitis, and exacerbates induced proximal colitis and fibrosis. Intestinal fibroblasts express Death-receptor 3 (DR3; the only know receptor for TL1A) and stimulation with TL1A induces activation in vitro. However, the contribution of direct TL1A-DR3 activation on fibroblasts to fibrosis in vivo remains unknown. TL1A overexpressing naïve T cells were transferred into Rag^-/- , Rag^-/- mice lacking DR3 in all cell types (Rag^-/-Dr3^-/-), or Ra

SUBMITTER: Jacob N 

PROVIDER: S-EPMC7584589 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature