Tfh细胞-B细胞功能性轴线在类风湿性关节炎发病中的作用及机制的研究

The over-activated humoral immunity has long been considered to be crucial in the pathogenesis of RA. Recently, a new CD4 helper T cell subset named follicle helper T cells (Tfh cells) was identified. Tfh cells are specifically distributed the follicle area of lymph node where they meet B cells and provide indispensable supports that covered all the major immunological activities of a B cell, the lack of Tfh cells leads to fatal defeat in the humoral immunity. The finding of Tfh cells , together with B cells, has thus formed a functional Tfh-B cell axis which may be the major content of humoral immunity. We now know little about the Tfh cells in RA,not only their function to B cells and humoral immunity,but the basic information such as their distribution,frequency,subtypes in different stage of RA.We thus proposed the current study to answer these questions. We also questioned a specific gene expression profile of rheumatic Tfh cells and its further applications as a therapeutic target of RA. We believe that our study will gain a major step forward to the total understood of RA and especially benefit the possible immunotherapies of RA.

异常亢进的体液免疫在类风湿性关节炎（RA）的发病中起关键作用，而近年来新发现的滤泡辅助性T细胞（Tfh）则是一种特异分布在淋巴滤泡内专职辅助B细胞的CD4T细胞。Tfh细胞的辅助涵盖B细胞所有的重要免疫学功能，而Tfh细胞-B细胞-体液免疫这一功能性轴线也就此浮出水面。目前对RA中Tfh细胞研究几乎处于空白阶段，我们前期发现Tfh在RA受累关节滑膜中异常增多，提示其致病作用，我们将在本项目中继续回答RA中Tfh的分布、数量、功能、亚群分布情况及如何通过B细胞的影响体液免疫等重要的问题。此外，我们还将研究RA中的病理性Tfh特异性基因表达谱，探索是否可以通过相关分子阻断Tfh治疗RA。我们的研究将填补RA研究中大块空白，为RA致病机制提供新的证据，也为RA的免疫治疗提供新思路。

异常亢进的体液免疫在类风湿性关节炎（RA）的发病中起关键作用，而近年来新发现的滤泡辅助性T细胞（Tfh）则是一种特异分布在淋巴滤泡内专职辅助B 细胞的CD4 T 细胞。Tfh 细胞的辅助涵盖B 细胞所有的重要免疫学功能，而Tfh 细胞-B 细胞-体液免疫这一功能性轴线也就此浮出水面。目前对RA中Tfh 细胞研究几乎处于空白阶段，我们前期发现Tfh 在RA 受累关节滑膜中异常增多，提示其致病作用，我们将在本项目中继续研究RA 患者及对照外周血受累关节膜组织Tfh 分布、数量表型及功能，并建立胶原诱导的关节炎小鼠模型，清除其体内Tfh 细胞，观察Tfh 细胞对其关节损伤的影响。我们的研究将填补RA 研究中大块空白，为RA 致病机制提供新的证据，也为RA 的免疫治疗提供新思路