T细胞受体（T cell receptor, TCR）是获得性免疫过程中的关键抗原识别分子。TCR通过本身多样的受体组库识别外源感染或内源突变抗原，而T细胞对自身抗原产生的免疫反应通常是引发自身免疫疾病的重要因素。我们之前的研究表明硫酸胆固醇（CS）作为胆固醇的天然代谢产物，可以抑制TCR信号，并影响T细胞发育过程中的胸腺选择，由此改变对自身抗原特异识别的成熟T细胞数量。本课题组将利用实验性自身免疫性脑脊髓炎（EAE）模型，在硫酸转移酶缺陷小鼠中深入研究病理条件下CS对T细胞的调控机制。并尝试在多发性硬化症（MS）患者中建立胆固醇代谢与自身免疫疾病的相关性，为开发基于代谢产物的免疫治疗方法提供新的理论基础。

T cell receptor (TCR) is responsible for recognizing foreign or mutant antigen to mount an adaptive immune response. To distinguish different antigens, a diverse TCR repertoire is generated by random recombination of discrete gene segments. Thus, T cell tolerance to self-antigens is equally important for the regulation of immune system, failure of maintaining immune homeostasis leads to the onset of autoimmune diseases. We have demonstrated the molecular mechanism on how cholesterol sulfate (CS), a naturally-occurring cholesterol metabolite, regulates TCR signaling, and elucidate its physiological impact in regulating T cell development and shaping the T cell repertoire against self-antigen. We will apply the experimental autoimmune encephalomyelitis (EAE) model to our newly established sulfotransferase (Sult2b1)-deficient mice to investigate how metabolites regulate the immune cell under pathological conditions. This study will also try to establish a relationship between human multiple sclerosis (MS) and cholesterol metabolism, and provide a theoretical foundation for developing metabolite-based therapeutic strategy to treat autoimmune disease.