从泛素连接酶调控T细胞外周耐受探讨狼疮定治疗SLE的作用机理

Systemic lupus erythematosus (SLE) is a relatively common systemic multi-organ involvement of multi-system autoimmune disease, and immune cells, especially closely related to the abnormal activation of T cells. In recent years, the study found that ubiquitin proteasome system (UPS) closely related to occurrence and development of SLE, particularly UPS played a key role in regulation of T cell tolerance.. Our research team found that Langchangding in the treatment of SLE has better clinical efficacy by long-term clinical observations and experimental studies, which can significantly reduce complications, reduce the level of SLEDAI, and adjust Peripheral lymphocytes andimmune factors have a significant role. However, it is not clear whether Langchangding has a regulatory role on ubiquitin-proteasome system (UPS), and whether by adjusting the ubiquitin- proteasome pathway induced peripheral T cell tolerance to treatment. Therefore, on the basis of previous studies, this study intends to through experiments in vivo and in vitro to explore whether Langchangding by adjusting the ubiquitin ligase - peripheral T cell tolerance loop to treat SLE. Firstly, we study the influence of Langchangding in regulation of peripheral T lymphocyte subtypes of cells and the expression of ubiquitin ligase Cbl-b or Itch from the overall level of animal research for lupus-like MRL/lpr mice. Secondly, we investigate the regulation of T lymphocyte by Langchangding after Cbl-b or Itch gene silence on the in vitro cellular level. In short, we will research the mechanism of Langchangding in the treatment of SLE from these two aspects, to clarify the therapeutic mechanism of traditional Chinese medicine in the treatment of SLE.

系统性红斑狼疮（SLE）是一种常见的自身免疫病，与免疫细胞，尤其是T细胞的异常活化密切相关。近年来研究发现泛素-蛋白酶体系统（UPS）与SLE的发生发展关系密切，而UPS对外周T细胞耐受起了关键的调控作用。. 本课题组长期研究发现，狼疮定治疗SLE具有较好的临床疗效，能显著减少并发症，有效降低SLEDAI，对免疫因子有显著调节作用，但狼疮定是否通过调节UPS途径从而诱导外周T细胞耐受来治疗SLE的，还不清楚。故在前期研究的基础上，本研究拟通过体内外实验探讨狼疮定是否通过调节泛素连接酶从而调控外周T淋巴细胞的耐受作用来治疗SLE的，即从整体动物水平研究狼疮定对MRL/lpr狼疮鼠外周T淋巴细胞亚型的调节及对细胞中泛素连接酶Cbl-b、Itch的影响，和体外细胞水平研究该方对经Cbl-b或Itch 基因沉默处理后的T淋巴细胞的调节作用，这两方面来探讨狼疮定治疗SLE的作用机理。

系统性红斑狼疮（SLE）是一种常见的自身免疫病，与免疫细胞，尤其是T细胞的异常活化密切相关。近年来研究发现泛素-蛋白酶体系统（UPS）与SLE的发生发展关系密切，而UPS对外周T细胞耐受起了关键的调控作用。本课题组长期研究发现，狼疮定治疗SLE具有较好的临床疗效，能显著减少并发症，有效降低SLEDAI，对免疫因子有显著调节作用，通过对本项目的研究，明确了狼疮定对MRL/lpr狼疮小鼠的治疗作用，揭示了狼疮定对泛素连接酶Cbl-b有调节作用，从全新的角度探讨了狼疮定治疗SLE的作用机制。