Th17细胞在宿主防御、炎症、自身免疫病中都起着至关重要的作用，研究Th17细胞的分化机制是揭示疾病发病机理的关键。Th17细胞可以分为TGF-β依赖型和TGF-β非依赖型。申请人的早期工作报道了SKI调控TGF-β依赖型Th17细胞分化的分子机制。而TGF-β非依赖型的Th17细胞在自身免疫病模型中有着极强的致病性特征，其分化机制尚未被揭示。申请人首先将其分成了两个细胞亚群：Activin介导的致病性Th17，和独立于TGF-β受体信号的被命名为tiTh17的细胞亚群。SKI通过不同的方式参与调控。申请人设计制作了多种工具鼠来研究TGF-β非依赖型Th17的分化机制。本项研究将鉴定出新的Th17细胞亚群和分化机制，为自身免疫病的治疗和药物筛选提供靶标。

Th17 cells are critically involved in host defense, inflammation and autoimmunity. The study of Th17 differentiation regulation mechanism is vital for understanding pathological process of diseases. Th17 cells can be classified as TGF-β-dependent and TGF-β-independent types. We previously reported the molecular program of SKI in regulating TGF-β-dependent Th17 cell differentiation. However, the differentiation of highly pathogenic TGF-β-independent Th17 cell is still elusive. We defined two subsets: Activin-mediated pathogenic Th17, and TGF-β receptor-independent Th17, named as tiTh17. SKI regulates these two subsets in different ways. We designed genetically modified mice to study the differentiation mechanisms. This study will identify new Th17 subsets and novel mechanisms, and will provide targets for drug screening and the treatment of autoimmune diseases.