多发性硬化症（MS）和实验性变态反应性脑脊髓炎（EAE）是由活化的Th1/Th17细胞亚群介导的自身免疫性疾病，但其发生机制仍不清楚。内质网接头蛋白Sel1L参与对细胞内质网（ER）中非正常折叠蛋白的降解、转运，并与ER内非正常折叠蛋白反应（UPR）、细胞自噬密切相关。本课题组前期研究发现，Sel1L分子缺失可影响Th1/Th17细胞亚群分化。因此，我们提出Sel1L调控CD4+T细胞亚群分化、参与此类疾病发生发展的科学假说。本研究将利用T细胞特异性Sel1L敲除小鼠，结合EAE模型，研究Sel1L分子对Th1/Th17亚群分化的调控效应及在EAE进程中的作用，并探讨Sel1L与UPR、细胞自噬在其中的效应与机制，以期阐明细胞ER内Sel1L分子对CD4+T细胞亚群分化调控机制，及在此类免疫性疾病中的作用；为CD4+T细胞亚群分化机制提供新理论，为MS疾病治疗寻找新靶点。

Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) are autoimmune demyelinating diseases which mediated by activated CD4+ T cells. Recently, published studies declared that unfolded protein response (UPR) and autophage did contribution to the development of these diseases, but its exact roles in the activation of autoimmune CD4+T have not been well demonstrated. In mammals, adaptor protein suppressor-enhancer of lin-12-like (Sel1L) works with other proteins to form a highly conserved complex ER-associated degradation (ERAD), which is a principle quality mechanism responsible for targeting misfolded ER proteins for cytosolic degradation. If the functions of ERAD were overloaded or deficient, UPR and autophage in cells will be activated. In this study, by using the CRISPR/Cas9 system, we generated T specific Sel1L deletion mice to explore the effects and the potential mechanisms of Sel1L mediate ERAD in the differentiation of CD4+ T subsets and the development of Experimental autoimmune encephalomyelitis (EAE), a widely used mice model of MS. If these were well demonstrated, it will not only be helpful to understand the differentiation of CD4+ T subsets better, but to find a new target for the treatment of MS.