肠道菌群调控记忆性Tfh细胞和记忆性B细胞亚群介导SLE/LN免疫紊乱的机制研究

Current studies reported that host intestinal flora changes are associated with the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis (LN). SLE is autoimmune disease characterized by abnormal expression of lymphocytes and disruption of peripheral immune tolerance. "Unbalanced flora" causes the pathogenesis of SLE is unknown. Our previous study found that the number and phenotypic changes of memory Tfh cells and B cell subsets in peripheral blood of patients with SLE are related to the activity of SLE; based on this, our hypothesis is: whether the intestinal flora regulates Memory Tfh cells help primary or memory B cells to differentiate into plasma cells, promote autoantibody production, and cause deposition of immune complexes leading to tissue and organ pathological damage; our study is intended to monitor changes of intestinal flora in patients with SLE/LN. To clear the relationship between changes of memory Tfh and memory B cell subpopulations with clinicopathological type in peripheral blood and pathological tissue, to elucidate that intestinal flora regulate memory Tfh cells and B cell subsets mediating SLE/LN immune disorder. To reveal the molecular mechanism of gut microbiota regulating immune B-cell and Tfh cell subsets mediating SLE/LN. It is beneficial to develop a new cell- and molecular-targeted drug for the treatment of SLE/LN from a new perspective, providing theoretical basis and experimental data for SLE/LN classification, diagnosis, and prognosis evaluation.

研究报道宿主肠道菌群改变与系统性红斑狼疮（SLE）及狼疮性肾炎（LN）的发病机制相关，SLE是一种以淋巴细胞表达异常、外周免疫耐受机制破坏为特征的，主要影响女性的自身免疫性疾病。“菌群失衡”导致SLE发病的机制不明。本课题组前期研究发现：SLE患者外周血中记忆性Tfh细胞和B细胞亚群的变化与SLE的活动性相关；基于此，提出的科学假设是：肠道菌群是否通过调控记忆性Tfh细胞辅助原始的或记忆性B细胞分化成浆细胞，促进自身抗体生成，免疫复合物沉积导致组织、器官病理损伤；本研究拟通过监测SLE/LN患者肠道菌群的变化、外周血及病检组织中记忆性Tfh和记忆性B细胞亚群的变化与临床病理分型的相关性，探讨肠道菌群调控记忆性Tfh细胞和B细胞亚群介导SLE/LN免疫紊乱的细胞、分子机制及相关临床意义；有利于从一个崭新的角度开发分型、诊断、预后评价和治疗SLE/LN新的肠道菌群、免疫细胞、分子靶向药物。

研究报道宿主肠道菌群改变与系统性红斑狼疮（SLE）及狼疮性肾炎（LN）的发病机制相关，SLE是一种以淋巴细胞表达异常、外周免疫耐受机制破坏为特征的，主要影响女性的自身免疫性疾病。“菌群失衡”导致SLE发病的机制不明。.我们的实验结论表明：.1.狼疮性肾炎患者肠道菌群的丰度和多样性低于SLE非肾炎患者，而SLE患者肠道菌群的丰度和多样性低又低于健康人群。SLE患者放线菌门和双歧杆菌属的丰度低于健康人群，变形杆菌门和志贺菌属的丰度高于健康人群。.2.SLE患者肾脏受累程度及狼疮性肾炎的的活动度与免疫细胞和血浆内细胞因子的比例相关，SLE非肾炎患者促炎性细胞因子表达高于狼疮性肾炎患者，抑制性炎症因子的表达低于狼疮性肾炎患者；狼疮性肾炎活动期患者的促炎性细胞因子表达高于缓解期患者，抑制性炎症因子的表达低于缓解期患者。.3.放线菌门和双歧杆菌属的丰度与正常人群和患者的免疫细胞和血浆内细胞因子、患者临床指标存在相关性。