前期研究发现，对TNFa抗体治疗有效的类风关患者，血浆中IL-7含量显著降低；对TNFa抗体治疗无效的类风关患者，血浆IL-7含量变化不明显，此现象提示IL-7在类风关发病中可能存在两种机制，即TNFa依赖和TNFa非依赖途径，IL-7或IL-7R可能是TNFa抗体治疗无效类风关患者的重要治疗靶点。但目前国内外免疫学家尚未对该治疗靶点做深入系统的研究。因此，本课题拟应用IL-7抗体和IL-7R抗体对IL-7/IL-7R信号通路进行阻断，通过体内（胶原诱导的关节炎模型）和体外（类风关标本）实验研究其治疗类风关的细胞和分子机制。创新点在于首次系统性探索阻断IL-7/IL-7R信号通路影响类风关发病机制中重要环节（包括致病性Th1和Th17细胞亚群、M1型巨噬细胞和炎症因子）的细胞和分子作用机理，研究结果将阐明类风关发病新机制，并为寻找类风关免疫干预新方案和新靶点提供理论和实验基础。

In previous study, it was observed that plasma IL-7 levels were significantly decreased in anti-TNFa responding rheumatoid arthritis patients, whereas levels of IL-7 were not reduced in non-responders. It suggests that there are two mechanisms of IL-7 in RA pathology: TNFa-dependent and TNFa-independent pathway. It suggests that IL-7 and IL-7 receptor may be important therapeutic targets in anti-TNFa non-responders. But, up to now, the therapeutic targets have not been completely elucidated. Therefore, the project we apply for this time is about cell and molecular mechanism study on rheumatoid arthritis by IL-7 antibody and IL-7R antibody therapy through in vivo (collagen-induced arthritis model) and in vitro (specimens from rheumatoid arthritis patients) experiments. The innovation point is that we firstly explore the cell and molecular mechanism of IL-7/IL-7R signalling pathway in the matter of key links in RA pathology (including pathogenic Th1 and Th17 cell subsets, macrophage M1 and inflammatory factors). It will contribute to elucidate new mechanisms, provide new therapeutic targets and treatment perscription for rheumatoid arthritis.