探讨Treg和Th17细胞的可塑性在重症肌无力免疫病理机制中的作用和临床价值

Our experimental results and previous studies have proved that increased cytokines of Th1 and Th17 cells play critical roles in MG and Treg cells in MG patient can express cytokine genes of Th1 and Th17 cells. This suggests that the cell plasticity may have a relationship with MG. Considering the plasticity of Treg and Th17 cells can mediate the occurrence and development of many autoimmune diseases by affecting immune balance and forming pathogenetic cells, we hypothesize that the plasticity of Treg and Th17 cells is involved in the immunopathology of MG. We intend to analyze the feature of T cell subsets which reflect the plasticity of Treg and Th17 cells by flow cytometry and find the correlation between clinical indicators and Treg or Th17 cells plasticity by statistic analysis. Then we will explore factors involved in regulating the expression of these T cell subsets by stimulating with cytokines or AChR peptides.Therefore, we can identify whether Treg and Th17 cells plasticity play a role in MG. This study will further elucidate the immunopathology of MG and find new laboratory indicators for the disease progression. What is more, it may provide a theoretical basis for immune-modulating therapy and specific therapeutic strategies targeting the plasticity of Treg and Th17 cells.

前期研究结果和文献表明重症肌无力患者体内Th1和Th17细胞相关因子表达增多并参与疾病的发生发展，而患者的Treg细胞又被证明可表达Th1和Th17细胞相关因子的基因，因而推断细胞可塑性有参与该疾病的可能，由于Treg和Th17细胞的可塑性可通过影响免疫平衡或形成致病性细胞介导自身免疫疾病的发生，由此我们提出假说：Treg和Th17细胞的可塑性参与自身免疫疾病重症肌无力的病理过程。本研究旨在通过流式细胞学等技术检测体现Treg和Th17细胞可塑性的T细胞亚群在重症肌无力中的特征，统计分析它们和临床指标的相关性，并采用乙酰胆碱抗原肽库刺激等手段探索这些细胞的调节表达因素，从而明确Treg和Th17细胞的可塑性是否参与以及如何参与重症肌无力的发生发展。本研究有助于完善重症肌无力的免疫病理机制，为预测疾病进展寻找新的实验指标，并为开发基于Treg和Th17细胞可塑性的免疫调节治疗提供理论依据。

重症肌无力（Myasthenia gravis，MG）患者体内Th1和Th17细胞相关因子表达增多并参与疾病的发生发展，而Treg细胞又被证明可表达促炎细胞相关因子的基因。本项目的目的在于探索Treg和Th17细胞的可塑性调控免疫平衡或形成致病性细胞的机制。在该项基金项目的执行过程中，我们检测了Th17与Treg细胞亚群的表达以及与临床指标的相关性，结果发现：外周血致病性Th17细胞可能是AChR-MG与MuSK-MG有效的生物标记物，且靶向抑制CD4+ T细胞的表面分子CD161，有望达到靶向治疗MG；外周血CD45RA-Foxp3++Treg细胞激活是诱导AChR-MG达到免疫耐受的重要机制；EAMG动物模型证实通过调节致病性Th17细胞/Treg细胞亚群的失衡有望治疗AChR-MG。通过精准干预Treg和Th17细胞的可塑性调节通路，有望实现MG的精准治疗。