“IL6-Tfh-B细胞”轴免疫调控异常在MOG抗体介导的视神经脊髓炎谱系病发病机制中的作用

有关MOG抗体（MOG-ab）介导的视神经脊髓炎谱系病（NMOSD）发病机制的研究极少。我们前期已证明NMOSD存在显著的调节性B细胞与记忆性B细胞免疫失衡。而滤泡辅助T（Tfh）细胞可在IL6的作用下，促进B细胞成熟、记忆形成及产生抗体，极可能是造成B细胞功能失衡的上游调控因素。进一步病理学研究证实MOG-ab+NMOSD患者脑部病灶内大量CD4+PD1+类Tfh浸润，同时脑脊液Tfh相关因子IL6水平亦显著升高。据此，我们提出IL6-Tfh-B细胞轴调控异常参与MOG-ab+NMOSD发病的假设，并拟通过体外细胞实验、MOG-EAE小鼠体内实验及血脑屏障模型通透性实验，逐层深入探讨Tfh如何在其上游因子IL6的作用下，经IL21依赖的途径调控B细胞参与MOG-ab+NMOSD的发生与发展，以期阐明MOG-ab+NMOSD的自身免疫机制，发掘潜在的治疗靶点。

The pathogenesis of MOG-ab mediated NMOSD is seldom investigated. Our previous investigation demonstrated that the functional imbalance between regulatory and memory B cell was involved in the pathogenesis of NMOSD. Recently, follicular helper T cell (Tfh) has been proved to possess the capability of helping B cell mature into memory B cell and antibody expressing plasma cell under the action of IL6, which indicates that Tfh may be a key upstream regulator of B cell. Our further pathological study revealed that a large number of Tfh like CD4+PD1+T cell infiltrated in the cerebral lesions of MOG-ab+NMOSD patients. The Tfh related cytokine IL6 was also elevated in the CSF of MOG-ab+NMOSD patients. Based on these findings, we speculate that IL6-Tfh-B cell pathway plays a key role in the development of MOG-ab+NMOSD. In the current study, we aim to elucidate how Tfh, under the action of IL6, cause the dysfunction of B cell through expressing IL21 in MOG-ab+NMOSD via in vitro cell culture, MOG-EAE model intervention and blood brain barrier model permeability experiment. In order to further clarify the pathogenesis of MOG-ab+NMOSD, and disclose potential therapeutic target.