类风湿关节炎（RA）成纤维样滑膜细胞（FLS）在炎性细胞招募、免疫炎症反应、病理损伤及关节破坏中介导主要的作用。我们前期研究发现炎性环境下RAFLS自分泌大量趋化因子CCL11，其受体CCR3表达也明显上调，进而促进基质金属蛋白酶（MMP）的表达，从而影响RAFLS的迁移和侵袭能力。据此提出科学假说：RAFLS通过自分泌CCL11介导滑膜炎症、软骨细胞活化和骨破坏，其确切的机制尚待进一步探讨。本项目拟通过原代细胞培养/共培养、小鼠胶原诱导型关节炎（CIA）模型和临床标本等，从细胞和分子水平以及应用慢病毒转染、阻断剂和抗体作用等进一步阐明FLS通过CCL11表达影响软骨破坏和骨侵蚀中发挥的作用及机制；评价CCL11/CCR3途径作为RA靶向治疗的价值，为进一步筛选免疫治疗靶点提供依据。

Fibroblast-like synoviocyte (FLS) in rheumatoid arthritis (RA) recuit inflammatory cells and cause immune inflammatory reactions which play an important role in the pathologic features of RA disease, such as cartilage destruction and bone invasion. Interactions between chemokines and their receptors were involved in the pathogenesis of RA process. Our previous study found that in inflammatory environment, plenty of CCL11 was expressed by RAFLS .The receptor of CCL11,CCR3 was increased significantly.The expression of matrix metalloproteinases (MMPs) was increased and CCL11/CCR3 interaction improved migration and invasion of RAFLS. We propose the scientific hypothesis: CCL11 / CCR3 pathway of RAFLS is important in the RA immunopathogenesis by regulating the expression of MMPs and participating in formation and activation of osteoclast. We will prove the hypothesis by culturing primary RAFLS with osteoclast precursor cells and using type II collagen induced arthritis (CIA) mice model to explore the molecular mechanisms of CCL11/CCR3 way in RA joint destruction by the application of CCR3 blockers and CCL11 antibody. We will further find how CCL11 / CCR3 pathway works in cartilage destruction and bone erosion of rheumatoid arthritis. Finally, CIA mice model will be used to evaluate CCL11/CCR3 blocdade as a potential therapy for rheumatoid arthritis. In summary, Interventions with these signals may contribute to immune homeostasis and offer potentially promising approach for the treatment of RA.