| First Author | Son A | Year | 2013 |
| Journal | Mucosal Immunol | Volume | 6 |
| Issue | 6 | Pages | 1131-42 |
| PubMed ID | 23462911 | Mgi Jnum | J:315297 |
| Mgi Id | MGI:6830033 | Doi | 10.1038/mi.2013.10 |
| Citation | Son A, et al. (2013) TWEAK/Fn14 pathway promotes a T helper 2-type chronic colitis with fibrosis in mice. Mucosal Immunol 6(6):1131-42 |
| abstractText | Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), a TNF superfamily member, induces damage of the epithelial cells (ECs) and production of inflammatory mediaters through its receptor Fn14 in a model of acute colitis. In our current study of chronic colitis induced by repeated rectal injection of a hapten, we found that inflammation, fibrosis, and T helper 2 (Th2)-type immunity were significantly reduced in Fn14 gene knockout (KO) mice when compared with wild-type (WT) control mice. Expression of thymic stromal lymphopoietin (TSLP) was lower in Fn14 KO colon ECs than in WT ECs. TWEAK potentiates the induction of TSLP by interleukin-13 (IL-13) in colon explants from WT but not in Fn14 KO tissue. TSLP receptor KO mice exhibit milder chronic colitis, similar to that in Fn14 KO mice. TWEAK and IL-13 synergistically promote fibroblast proliferation. Thus we propose an IL-13-TWEAK/Fn14-TSLP axis as a key mechanism underlying chronic colitis with fibrosis. |
