Classical Th1 cells obtain colitogenicity by co-existence of RORγt-expressing T cells in experimental colitis
Classical Th1 cells obtain colitogenicity by co-existence of RORγt-expressing T cells in experimental colitis
复制标题
经典 Th1 细胞通过在实验性结肠炎中与表达 RORγt 的 T 细胞共存而获得结肠原性
DOI：
10.1097/mib.0000000000000149
复制
发表时间：
2014
影响因子：
4.9
通讯作者：
Kanai T
中科院分区：
文献类型：
--
作者：
Saigusa K;Hisamatsu T;Handa T;Sujino T;Mikami Y;Hayashi A;Mizuno S;Takeshita K;Sato T;Matsuoka K;Kanai T
背景Th1和Th17细胞类型均参与慢性肠道炎症的发病机制。我们最近证明，表达类维生素A相关孤儿受体γt（RORγt）的Th17细胞是替代性Th1细胞的祖细胞，其有可能诱发结肠炎。然而，直接从不表达 RORγt 的幼稚 T 细胞产生的经典 Th1 (cTh1) 细胞在结肠炎发病机制中的作用仍知之甚少。 方法我们使用通过将野生型、RORγtgfp/gfp 或 RORγtgfp/+ 小鼠获得的脾 CD4+CD45RBhighT 细胞过继转移到小鼠慢性结肠炎模型中进行了一系列体内实验。 RAG-2−/−小鼠。结果接受体外操作的 RORγtgfp/gfpTh1 细胞转移的 RAG-2−/−小鼠出现结肠炎。与从 RORγtgfp/gfpmice 获得的脾 CD4+CD45RBhighT 细胞移植的非结肠炎小鼠相比，与从野生型小鼠和 RORγtgfp/gfpmice 获得的脾 CD4+CD45RBhighT 细胞共移植的 RAG-2−/− 小鼠出现结肠炎，且 RORγtgfp/gfpcTh1 细胞数量显着增加。此外，体内操作的 RORγtgfp/gfpcTh1 细胞转移的 RAG-2−/− 小鼠出现结肠炎，且 RORγtgfp/gfpcTh1 细胞数量显着增加。结论这些发现表明，替代 Th1 细胞和 cTh1 细胞在适应性转移模型中都有可能产生结肠炎。 cTh1 细胞的发育依赖于表达 RORγt 的 T 细胞的共存，这表明这些细胞类型的相互作用在慢性肠道炎症的发展中发挥着关键作用。
BackgroundBoth Th1 and Th17 cell types are involved in the pathogenesis of chronic intestinal inflammation. We recently demonstrated that retinoid-related orphan receptor gamma t (RORγt)-expressing Th17 cells are progenitor cells for alternative Th1 cells, which have the potential to induce colitis. However, the involvement of classical Th1 (cTh1) cells generated directly from naive T cells without RORγt expression in the pathogenesis of colitis remains poorly understood.MethodsWe performed a series of in vivo experiments using a murine chronic colitis model induced by adoptive transfer of splenic CD4+CD45RBhighT cells obtained from wild-type, RORγtgfp/gfp, or RORγtgfp/+mice into RAG-2−/−mice.ResultsRAG-2−/−mice receiving transfer of in vitro-manipulated RORγtgfp/gfpTh1 cells developed colitis. RAG-2−/−mice co-transferred with splenic CD4+CD45RBhighT cells obtained from wild-type mice and RORγtgfp/gfpmice developed colitis with a significant increase in RORγtgfp/gfpcTh1 cell numbers when compared with noncolitic mice transferred with splenic CD4+CD45RBhighT cells obtained from RORγtgfp/gfpmice. Furthermore, RAG-2−/−mice transferred with in vivo-manipulated RORγtgfp/gfpcTh1 cells developed colitis with a significant increase in RORγtgfp/gfpcTh1 cell numbers.ConclusionsThese findings indicate that both alternative Th1 cells and cTh1 cells have the potential to be colitogenic in an adaptive transfer model. The development of cTh1 cells was dependent on the co-existence of RORγt-expressing T cells, suggesting a critical role for the interactions of these cell types in the development of chronic intestinal inflammation.