浆细胞样树突状细胞（pDC）-I型IFN系统诱导多发性肌炎模型大鼠骨骼肌细胞损伤的分子机制

Polymyositis is an autoimmune disease mainly involving in the skeletal muscle that often with pathological features of the cell degeneration and necrosis meanwhile CD8 T cells/MHC-I complex emerged. The pathogenesis of polymyositis is not clear. The abnormalities of cellular immune, the abnormal of cytokine expression and the disorder of apoptosis mechanism may be contribute to. In the recent years, the research of PM is slow and lack of an key to put all together. Plasmacytoid dendritic cells(pDC) is the main body of type I-interferon producing cells. It also has immunomodulatory, antigen presentation, and many other effects. This research will use a rat model of PM as research tool and put pDC as the core. The aim is to prove that activated peripheral blood pDC of PM rats will migrate gradually to the skeletal issue and produce a lot of type I-IFN, then induce the up expression of MHC-I molecules on skeletal muscle cells, stimulate the CD8 T lymphocyte to be activated and proliferate, and get the ability to induce skeletal muscle apoptosis after up expressing TRAIL. So we can known well about the molecular mechanism of plasmacytoid dendritic cells (pDC) - I interferon system killing skeletal muscle cell of polymyositis rats.

多发性肌炎是一类以骨骼肌病变为主的自身免疫性疾病，其病理特点是受累骨骼肌的变性、坏死和病变局部CD8 T淋巴细胞/MHC-Ⅰ类分子复合物的出现，其发病机制目前并不清楚，细胞免疫异常、局部细胞因子表达异常、凋亡相关机制紊乱均可能参与其中，但近年来的相关研究进展较慢，缺少关键因素能将上述机制有机结合起来。浆细胞样树突状细胞(pDC)是体内主要的I型IFN产生细胞，同时还具有免疫调节、抗原呈递等多方面功效，是固有免疫和获得性免疫之间的重要桥梁。本课题以PM大鼠模型为研究工具，以pDC-I型IFN系统为研究核心，证明多发性肌炎大鼠成模过程中外周血pDC逐渐活化、迁移到骨骼肌病变局部并大量产生I型IFN后能够上调骨骼肌细胞MHC-I分子表达、刺激CD8 T淋巴细胞的活化和增殖、高表达TRAIL诱导骨骼肌细胞凋亡，从而揭示pDC-I型IFN系统诱导多发性肌炎模型大鼠骨骼肌细胞损伤的分子机制。