通常认为胞内代谢为免疫细胞的分化提供了能量来源及生物合成前体。本课题组先前的研究表明胞内代谢能够和表观遗传以及转录密切结合来调控TH17细胞的命运决定，说明代谢不仅仅提供能量和生物合成前体，还具有“信号”功能。同时，我们还发现诱导TH17分化的细胞因子能够通过非TCR信号通路依赖的方式诱导谷草转氨酶（Got1）的表达，且为TH17细胞分化所必需，但其机制仍然不明。本项目中，我们将着力于阐明细胞因子信号是如何诱导Got1的表达进而调控TH17细胞的分化，也将探讨靶向代谢通路是否可以作为一个针对TH17细胞所介导的自身免疫性疾病的全新方法。我们的研究将会证明细胞因子不仅仅能通过信号通路来调控转录因子，还能调控代谢重编程从而促进T细胞的命运决定，并揭示在TH17细胞分化过程中STAT3如何下调FOXP3的表达，这一长期悬而未决的问题，并有望为TH17细胞所介导的自身免疫性疾病提供全新的药物靶点。

Intracellular metabolism is essential for the differentiation of immune cells by meeting their bioenergetic and biosynthetic demands. We have demonstrated that metabolism can integrate with epigenetics and transcription to control TH17 cell fate. Our recent data show that cytokines required for TH17 differentiation（IL-1β, IL-6 and IL-23）selectively regulate Got1 expression independent of TCR signaling, critical for TH17 cell development, however, the mechanism for which is still unknown. In this study, we will use multiple methods to uncover how these cytokines control Got1 expression and determine if targeting metabolic pathway is a valid strategy for TH17 cell mediated autoimmune diseases. Our study will demonstrate that cytokines required for TH17 differentiation ( IL-1β, IL-6 and IL-23) not only regulate transcription factor but also regulate metabolic reprogramming to promote T cell differentiation, and uncover the mystery of how STAT3 down-regulates FOXP3 expression during TH17 cell differentiation. In addition, our study will provide novel targets for TH17 cell mediated autoimmune diseases.