炎性肌病的发病机制仍不明确。文献报道和本课题组前期研究提示，骨骼肌细胞是免疫功能的积极参与者，但具体机制不明。我们提出假说：肌炎患者骨骼肌细胞分泌趋化因子定向吸引炎症细胞浸润至骨骼肌组织；microRNA调控肌细胞自身抗原的表达；肌细胞提呈自身抗原至细胞表面，活化浸润的淋巴细胞；肌细胞主导的免疫微环境使得炎症细胞增殖、分化以及持续活化；而炎症细胞分泌细胞因子或直接作用于肌细胞，通过免疫学机制和非免疫学机制造成肌细胞损伤。本研究拟从转录组学揭示各种自身抗原、细胞因子、趋化因子在炎性肌病骨骼肌细胞中的表达；阐明肌炎患者肌细胞定向趋化炎症细胞的能力；明确microRNA调控自身抗原表达的分子机制及骨骼肌细胞提呈抗原的能力；细胞共培养和RNA干扰技术研究骨骼肌细胞-炎症细胞之间相互作用机制；利用动物模型研究炎性浸润的早期事件及干预策略。从而阐明骨骼肌组织的免疫特性及其在炎性肌病发病机制中的作用。

The pathogenesis of idiopathic inflammatory myopathy remains to be fully elucidated. Literature reports and our previous findings indicate that skeletal muscle cells are emerging as an active player in immune functions. However, the precise mechanism remains unclear. We proposed a hypothesis that the muscle cells of inflammatory myopathy patients could trigger inflammatory cells mobilization to muscle tissue, and present autoantigens onto the cell membrane, resulting the proliferation, differentiation, activation of inflammatory cells. microRNAs participate in the regulation of autoantigen expression in skeletal muscle cells. The inflammatory cells consequently contribute to the skeletal muscle injury through immune mechanism and nonimmune mechanism. By transcriptome analysis, the mRNA expression levels of autoantigens, cytokines, chemokines in muscle tissue will be revealed. The role of myoblast in inflammatory cell mobilization will be studied via RNA interfering technology and cell co-culture technology. In the mean time, the mechanism of regulation in autoantigen expression by microRNA will be studied. The antigen presenting ability of myoblast will be investigated in idiopathic inflammatory myopathy patients. RNA interfering technology and cell co-culture technology will be used to study the interaction between muscle cells and inflammatory cells. Additionally, myositis animal models will be applied to carry out in vivo interventions and clarify the early progress of infiltration in muscle tissue. Taken together, the study may hopefully clarify the immunological characteristics of skeletal muscle tissue and its possible pathogenic role in idiopathic inflammatory myopathy.