我们前期研究发现在DSS诱导结直肠炎模型和体外诱导Treg细胞分化中，PI3K非经典调节亚基p55PIK可抑制Treg的分化，但其机制不详。我们在肿瘤研究中证实TGF-β可下调p55PIK的表达，而p55PIK又可以非Akt依赖方式募集并促进STAT3磷酸化。已知STAT3负调Treg分化，故我们推测p55PIK可能通过STAT3抑制Treg分化。本项目拟通过体内外实验阐明：① p55PIK以非Akt依赖方式促进STAT3磷酸化而负调Treg分化。②TGF-β通过抑制p55PIK/STAT3，与IL-2协同促进Treg分化。③用T细胞条件性敲除p55PIK小鼠以及临床IBD标本，观察p55PIK/STAT3对Treg细胞分化和炎性肠病的影响。该研究不但可阐明PI3K非经典途径在Treg分化中的作用，为TGF-β促进Treg分化提供新的分子机制，而且为防治IBD等自身免疫病提供新的靶点。

p55PIK was non-classical regulatory subunit in PI3K signaling. In previous study, we found that p55PIK inhibit Treg differentiation both in DSS-induced colitis mice model and in vitro Treg differentiation model, but the mechanism remains to be elucidated. We also found that TGF-β decreases the expression of p55PIK, whereas p55PIK recruits STAT3 and promote the phosphorylation of STAT3 in an Akt-independent pathway in tumor cell lines. It is reported that STAT3 could negatively regulate Treg differentiation, so we hypothesized that p55PIK could inhibit Treg differentiation through STAT3. The project aim to investigate: ① p55PIK inhibit Treg cell differentiation by STAT3 phosphorylation in an Akt-independent pathway. ② TGF-β cooperate with IL-2 to promote Treg differentiation through inhibiting p55PIK/STAT3.③ The effect of p55PIK/STAT3 on Treg differentiation and inflammatory bowel diseases(IBD), using T cell conditional p55PIK knockout mice model and clinical IBD samples. This study demonstrate the role of PI3K non-classical pathway in Treg differentiation, and provide the novel target for the therapy of autoimmune diseases, e.g IBD.