胸苷酸合成酶对炎症性肠病中T辅助细胞17的分化调节机制

The relationship of immune imbalance mediated by T helper cells and inflammatory bowel disease(IBD) have been the focus of significant recent studies. We found the basal expression of TS varies significantly between T helper phenotypes and knockdown of TS significantly impairs Th17 and Th1 cell differentiation without affecting the differentiation of either Treg or TH2 cells. Low dose 5-FU which is targeting TS and TS knockdown is effective in ameliorating colitis development by suppressing Th17 and Th1 cell development in a T cell transfer colitis model.However, the human expression of TS in T helper cells need to be investigated, and we will characterize the function of TS in human Th17 cell differentiation and explore the functional and physical interactions between TS and RORC2, may provide a potential Therapeutic targets for IBD patients.

T辅助细胞17（Th17）被认为是介导炎症性肠病（IBD）炎症反应的重要细胞。Th17细胞在免疫应答中的分子学调控机制有待进一步研究。我们前期研究证实了在小鼠原代细胞中敲低腺苷酸合成酶（TS)基因能抑制Th17细胞的分化；同样我们在人Th17细胞中也发现了和维甲酸相关孤核受体γt（RORγt）的同源结构分子RORC2表达，并且能诱导血中CD4+T细胞分泌IL-17A和IL-17F，而在IBD病人中TS能否调节Th17细胞的分化尚未明确。本研究拟收集IBD病人外周血及肠粘膜标本，来检测IBD病人人体的T辅助细胞的TS本底表达水平，体外用TS抑制剂或用siRNA敲低TS表达或TS过表达质粒转染调高TS表达等干预来检测TS对IBD病人Th17细胞分化的作用，采用免疫共沉淀等方法探索TS调节Th17细胞分化的机制，旨在阐明机制及为IBD寻找治疗靶点提供理论依据。