皮肤间充质干细胞通过其分泌的sTNFR1抑制Th17细胞的分化

项目名称： 皮肤间充质干细胞通过其分泌的sTNFR1抑制Th17细胞的分化

项目编号： No.31500730

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 柯芳

作者单位： 上海交通大学

项目金额： 20万元

中文摘要： Th17细胞在MS（multiple sclerosis）和EAE（experimental autoimmune encephalomyelitis）疾病发生发展过程中扮演重要角色。目前关于调控Th17细胞诱导分化的相关因子还知之甚少。MSCs能够抑制Th17细胞的分化和治疗自身免疫性疾病。尽管已经鉴定出一些MSCs分泌的免疫调节分子，但MSCs分泌的其他一些抑制Th17细胞分化的细胞因子还不清楚。我们前期的研究结果显示注射SMSCs可以治疗EAE，SMSCs能够抑制Th17细胞的分化，SMSCs活化后能产生高水平的sTNFR1，本项目主要调查sTNFR1对Th17细胞分化的影响以及与sTNFR1特异性结合的TNF-α对Th17细胞和抗原提呈细胞（APCs）的调控作用，最终揭示SMSCs治疗自身免疫性疾病的新机制。

中文关键词： 间充质干细胞；自身免疫性疾病；Th17细胞

英文摘要： T helper 17 (Th17) cells play an important role in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). However, much remains unclear about the regulatory factorscontrolling the differentiation of Th17 cells. Mesenchymal stem cells (MSCs) have emerged as a promising candidate for inhibiting Th17 cell differentiation and autoimmune diseases. Despite several molecules have been linked to the immunomodulatory function of MSCs, many of other key MSC-secreted regulators that are involved in inhibiting Th17 cell polarizationare ill defined. In our previous study, we demonstrated that the intraperitoneal administration of skin-derived MSCs (S-MSCs) suppressed the development of EAE in mice. Moreover, under an inflammatory condition we demonstrated that S-MSCs produced high amount of soluble TNF receptor 1 (sTNFR1) which binds TNF-α, In this project, we focused on the function of sTNFR1 on the differentiation of Th17 cells and the role of TNF-α on the modulation of Th17 cells and APCs. Thus, our data will uncover a previously unrecognized mechanism for MSCs therapy in autoimmune diseases.

英文关键词： mesenchymal stem cells;autoimmune diseases;Th17 cells