T细胞在免疫应答和自身免疫与炎症疾病中具有重要的调节作用。Th1和Th17细胞的过度活化可诱发多发性硬化症（Multiple sclerosis，MS）。利用CD4+T细胞体外分化体系进行化合物筛选，并对筛选出的具有抑制活性的化合物进行结构改造，最终得到新型小分子化合物TPN10456。我们发现TPN10456明显抑制Th17细胞分化。因此我们假设：TPN10456通过调控靶基因的功能从而抑制Th17细胞分化，进而缓解MS发病。为证明假设，本项目拟首先分析TPN10456对EAE的治疗作用；其次利用基因芯片和质谱技术筛选TPN10456调控Th17细胞分化的靶基因；最后利用基因敲除技术结合体外分化体系明确靶基因介导TPN10456调控Th17细胞分化的分子机制。本项目将揭示小分子化合物TPN10456调控Th17分化在MS发病中的作用和机制，为MS的基础研究和临床治疗提供理论依据。

T cells play an important role in the regulation of immune response and autoimmune and inflammatory disease. Excessive activation of Th1 and Th17 cells can cause multiple sclerosis (MS). We used the in vitro differentiation system of CD4+ T cells to screen the compounds, and modified the structure of the selected and good inhibitory activity compounds. We finally obtain a new small-molecule compound TPN10456. We found that TPN10456 significantly inhibited the differentiation of Th17 cells. Therefore, we assume that TPN10456 could inhibit the differentiation of Th17 cells by regulating the function of target genes to alleviate the pathogenesis of MS. In order to prove this hypothesis, we first analyzed the therapeutic effect of TPN10456 on EAE, and then screened the target genes of TPN10456 regulating the differentiation of Th17 cells by gene chip and mass spectrometry. Finally, gene knockout technique combined with cell differentiation system in vitro were used to identify the specific molecular mechanism of target gene mediated TPN10456 to regulate the differentiation of Th17 cells. This study investigating the role and mechanism of the small-molecular compound TPN10456 regulated Th17 differentiation in the pathogenesis of MS will provide theoretical basis for the basic research and clinical treatment of MS.