多发性硬化是一种经典的自身免疫性脱髓鞘疾病，至今尚无法治愈。小胶质细胞作为中枢神经系统固有免疫的重要组分和固有免疫与获得性免疫的桥梁，与多发性硬化的早期病理发生和神经退行性变性密切相关。改变体内小胶质细胞的极化方向可能是以小胶质细胞为靶点治疗多发性硬化的关键点。我们发现，同源盒基因MSX3可以促进体外培养小胶质细胞的M2极化，并提高小胶质细胞促进少突胶质前体细胞成熟的能力。在神经系统脱髓鞘疾病模型中，MSX3基因干扰可以阻断IL-4预刺激小胶质细胞脑内移植对神经功能的修复作用，并加重脱髓鞘损伤和炎细胞浸润。拟在此基础上，深入研究MSX3对体内小胶质细胞的作用及对神经系统脱髓鞘疾病的治疗作用，并探索MSX3促进M2极化的分子机制。我们对同源盒基因MSX3免疫调节新功能的发现，不仅为神经免疫调节提供新的分子机制，而且为神经系统脱髓鞘疾病的治疗提供新的靶点。

Multiple sclerosis is a classic autoimmune demyelinating disease. Microglia is an important component of CNS innate immune system and the bridge between the innate immunity and acquired immunity. They are closely related to the pathogenesis of multiple sclerosis. Changing the direction of microglial polarization in vivo is one of the key points on microglia as the target for the treatment of multiple sclerosis. Our previous studies shown that the homeobox gene MSX3 could promote M2 polarization of microglia, inhibit M1 polarization and further promote maturation of oligodendrocyte precursor cells (OPCs). Transplantation of MSX3 RNAi microglia into the brain ventricles can block the effects of IL-4 pre-stimulated microglia on neural repair in autoimmune demyelinating disease. On this basis of the present studies, we plan to verify the role of MSX3 on microglia and autoimmune demyelinating disease, and further explore the molecular mechanisms of MSX3 in promoting STAT6 and PPARγ expression and M2 polarization. Our findings of the new features of the homeobox gene MSX3 in immune regulation, not only to provide a new molecular mechanism of neuroimmunomodulation, but also provide new molecular targets for the treatment of autoimmune CNS demyelinating diseases.