Th17细胞分化异常和多种自身免疫性疾病有关，也是近年来免疫学研究热点之一。文献报道系统性红斑狼疮病人外周血T细胞中PP2A表达及活性增高。在小鼠T细胞中过表达PP2A可使IL-17分泌增加和对自身免疫性肾损伤敏感性增加。我们由此推测PP2A过度活化可能通过促进Th17细胞分化来增加对自身免疫性疾病的易感性。我们构建了T细胞特异性PP2A条件性敲除小鼠，发现T细胞中敲除PP2A导致CD4+ T细胞向Th17细胞分化能力明显减弱，MOG多肽诱导的小鼠EAE发病率和发病程度显著下降。本课题将在此基础上，进一步明确PP2A在Th17分化过程中的调控作用，深入研究PP2A在Th17分化过程中的调控机制，包括揭示可能参与的具体信号调控事件、寻找其作用靶标、明确其催化的磷酸化修饰位点等。本项目的完成有望为现有的Th17分化调控机制提供补充，同时为寻找新的药物靶点治疗自身免疫性疾病提供理论依据。

Dysregulation of Th17 differentiation is linked to the initiation and pathogenecity of various autoimmune diseases. Previous clinical researches have revealed higher expression level and catalytic activity of PP2A in peripheral T cells from SLE（Systemic Lupus Erythematosus）patients than those from healthy controls. Similarly, forced overexpression of PP2A in mice increased their susceptibilities to autoimmune glomerulonephritis due to elevated IL17 production. We thus hypothesize that excessive activation of PP2A might increase autoimmune disease susceptibility through promoting Th17 differentiation. Indeed, we observed decreased Th17 differentiation and EAE development in PP2A conditional knockout mice. This proposal will continue our study to illustrate the mechanisms how PP2A regulate Th17 differentiation. Our results may help the development of new therapeutic strategy for Th17 related autoimmune diseases.