外泌体转运Bcl9介导骨骼肌损伤在多发性肌炎/皮肌炎中的作用机制研究

多发性肌炎/皮肌炎（PM/DM）属自身免疫性疾病，表现有皮损及骨骼肌损害，发病机制复杂。近年发现外泌体在自身免疫性疾病中扮演重要角色。我们前期研究发现：PM/DM外泌体中蛋白exo-Bcl9高表达，生物信息学Gene Ontology预测Bcl9主要涉及骨骼肌损伤；进一步探索显示PM/DM受累骨骼肌组织中Bcl9呈外源性高表达，共培养实验发现PM/DM来源外泌体可侵袭骨骼肌细胞。因此提出假说：exo-Bcl9以外泌体转运形式侵袭损伤骨骼肌细胞，促进PM/DM发生。本课题将从临床样本、细胞水平、动物实验三个层面研究exo-Bcl9介导的免疫细胞与骨骼肌细胞间通讯，阐释外泌体参与的PM/DM发病新机制，并初步评估exo-Bcl9对PM/DM的临床诊断应用价值，有望为PM/DM提供诊断新靶标和治疗新思路。

Polymyositis/dermatomyositis (PM/DM) is an autoimmune disease characterized by skin and skeletal muscle lesions, and the pathogenesis has not been entirely cleared. Recent years, exosomes have been found to play an important role in the development of autoimmune diseases. Our previous study indicated that: exo-Bcl9, exosome-carried protein, was highly enriched in serum exosomes of PM/DM patients; Bcl9 was predicted to participate in skeletal muscle cell lesions through bioinformatics Gene Ontology analysis; Bcl9 was exogenous high expressed in PM/DM skeletal muscle tissues,co-culture experiment showed that the skeletal muscle cells were invaded by the PM/DM exosomes. Based on the previous study, we hypotheses that Bcl9, which carried by exosome, can affected human skeletal muscle cells(HskMC) in PM/DM. To identify this hypothesis, we will investigate the role and molecular mechanism of exo-bcl9 in PM/DM by employing human sample, cell and mice model. Our aim is to elucidate the mechanism of skeletal muscle lesions mediated by exo-Bcl9 in PM/DM, which is expected to provide new targets and ideas for PM/DM diagnosis and treatment.