Th22/IL-22通过JAK-STAT信号通路介导麻风神经损伤的免疫机制研究

麻风分枝杆菌的嗜神经性是其区别于其它分枝杆菌的独有特性，也是导致患者畸残的主要原因，具体机制尚不明确。已知Th22/IL-22可通过JAK-STAT通路调节神经炎症、促细胞凋亡等作用参与多种神经系统疾病的发病。申请人前期发现麻风菌体外刺激患者PBMC可致IL-22水平明显上升，免疫组化、qPCR示麻风患者皮损中IL-22较其它分枝杆菌感染皮损显著增多，且聚集于皮神经周围，提示IL-22可能为麻风神经损伤的关键细胞因子。进一步研究发现麻风皮损中JAK-STAT通路的p-STAT1、p-STAT3及一氧化氮合酶（iNOS）表达明显升高，推测IL-22可通过该通路调控神经细胞的增殖和凋亡。基于以上研究结果申请人拟通过细胞分离培养与刺激、单细胞测序等体外实验并利用IL-22基因敲除动物模型等体内实验进一步验证Th22/IL-22在麻风神经损伤的作用机制，为治疗提供新的理论依据。

The neurotropism of Mycobacterium leprae is a unique characteristic that distinguishes it from other mycobacteria and is also the main cause of deformity in patients. The specific mechanism is still unclear. Th22/IL-22 is known to be involved in a variety of neurological diseases by regulating neuroinflammation and promoting apoptosis through the JAK-STAT pathway. We found that PBMC stimulation of M. leprae in vitro could significantly increase the level of IL-22 in patients, and immunohistochemistry and qPCR showed that the skin lesions of leprosy patients were significantly higher than those of other mycobacterium infected skin lesions, and IL-22 was concentrated around the cutaneous nerve, suggesting that IL-22 may be a key cytokine in the injury of nerve in leprosy.Further studies found that the expressions of p-STAT1, p-STAT3 and iNOS in the JAK-STAT pathway in leprosy lesions were significantly increased, suggesting that IL-22 could regulate the proliferation and apoptosis of nerve cells through this pathway. Based on the above results, the applicant intends to further verify the mechanism of Th22/IL-22 in leprosy nerve injury through in vitro experiments such as cell isolation, culture and stimulation, single cell sequencing, and in vivo experiments such as animal model knockout of IL-22 gene, so as to provide new theoretical basis for treatment.