TL1A blocking ameliorates intestinal fibrosis in the T cell transfer model of chronic colitis in mice

Publication date: Available online 26 November 2017
Source:Pathology - Research and Practice
Author(s): Hui Li, Jia Song, Guochao Niu, Hong Zhang, Jinbo Guo, David Q. Shih, Stephan R. Targan, Xiaolan Zhang
Tumor necrosis factor like cytokine 1A (TL1A) is a member of the TNF superfamily. Accumulating evidence demonstrated the importance of TL1A in the pathogenesis of inflammatory bowel disease (IBD) and suggested a potential role of TL1A blocking in IBD therapy. Here we aimed to explore whether the anti-TL1A antibody could ameliorate intestinal inflammation and fibrosis in IBD. A T cell transfer model of chronic colitis was induced by intraperitoneal injection of CD4⁺CD45RB^high naive T cells isolated from either C57BL/6 wild type (WT) mice or LCK-CD2-Tl1a-GFP transgenic (L-Tg) mice into recombinase activating gene-1-deficient (RAG^−/−) mice. The colitis model mice were treated prophylactically or therapeutically with anti-Tl1a antibody or IgG isotype control. Haematoxylin and eosin staining (H&E staining), Masson's trichrome staining (MT staining) and sirius red staining were used to detect histopathological changes in colonic tissue, immunohistochemical staining was used to detect the expressions of collagen I, collagen III, TIMP1, Vimentin, α-SMA and TGF-β1/Smad3. Results showed that anti-TL1A antibody could reduce intestinal inflammation and fibrosis by inhibiting the activation of intestinal fibroblasts and reducing the collagen synthesis in the T cell transfer model of chronic colitis. The mechanism may be related to the inhibition of TGF-1/Smad3 signaling pathway.



http://ift.tt/2Be5vGx