TL1A blocking ameliorates intestinal fibrosis in the T cell transfer model of chronic colitis in mice
TL1A blocking ameliorates intestinal fibrosis in the T cell transfer model of chronic colitis in mice
复制标题
TL1A 阻断可改善小鼠慢性结肠炎 T 细胞转移模型中的肠纤维化
DOI：
10.1016/j.prp.2017.11.017
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发表时间：
2018-02-01
影响因子：
2.8
通讯作者：
Zhang, Xiaolan
中科院分区：
文献类型：
--
作者：
Li, Hui;Song, Jia;Zhang, Xiaolan
肿瘤坏死因子样细胞因子1A（TL 1A）是TNF超家族的成员。越来越多的证据表明TL 1A在炎症性肠病（IBD）发病机制中的重要性，并提示TL 1A阻断在IBD治疗中的潜在作用。本研究旨在探讨抗TL 1A抗体能否改善IBD患者的肠道炎症和纤维化。通过将从C57 BL/6野生型（WT）小鼠或LCK-CD 2-Tl 1a-GFP转基因（L-Tg）小鼠分离的CD 4（+）CD 45 RB（高）初始T细胞腹膜内注射到重组酶激活基因-1缺陷（RAG（-/-））小鼠中诱导慢性结肠炎的T细胞转移模型。用抗T11 a抗体或IgG同种型对照对结肠炎模型小鼠进行预防性或治疗性处理。采用苏木精-伊红染色（H&E染色）、Masson三色染色（MT染色）和天狼星红染色检测结肠组织的组织病理学变化;免疫组化染色检测I型胶原、III型胶原、TIMP 1、波形蛋白、α-SMA和TGF-β 1/Smad 3的表达。结果表明，在慢性结肠炎T细胞转移模型中，抗Tl 1a抗体可通过抑制肠道成纤维细胞的活化，减少胶原合成，减轻肠道炎症和纤维化。其机制可能与抑制TGF-1/Smad 3信号通路有关。
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, alpha-SMA and TGF-beta 1/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.