Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Adv Immunol. 2012;115:45-71. doi: 10.1016/B978-0-12-394299-9.00002-3.
Rheumatoid arthritis (RA) is an autoimmune disease, characterized by chronic inflammation and synovial hyperplasia in the joints that ultimately lead to cartilage and bone destruction. A wealth of research has shown that CD4(+) T cells, especially IL-17 producing helper T (Th17) cells, play an important role in RA development. However, it still remains to be clarified how the systemic immune response results in the local joint disorders. Studies on animal models of RA have shed light on the importance of the interaction between immune cells and joint-specific mesenchymal cells. In particular, joint-specific mesenchymal cells contribute to the Th17-mediated augmentation of the inflammatory phase in RA by promoting the migration of Th17 cells to the inflammatory joint and then homeostatic proliferation with increase in IL-17 production. In addition, recent progress in osteoimmunology has provided new insights into the pathogenesis of the bone destruction phase in RA. Of note, Th17 cells have been shown to enhance the differentiation of osteoclasts via joint-specific mesenchymal cells. Thus, the interaction of CD4(+) T cells and nonhematopoietic mesenchymal cells in joints plays a key role in RA pathogenesis during both the inflammatory and bone destruction phases. Focusing on this interaction will lead to a better understanding of the mechanism by which the systemic immune response results in local joint disorders and also helps provide a molecular basis for novel therapeutic strategies.
类风湿关节炎（RA）是一种自身免疫性疾病，其特征为关节慢性炎症和滑膜增生，最终导致软骨和骨破坏。大量研究表明，CD4+T 细胞，特别是产生白介素-17 的辅助性 T（Th17）细胞，在 RA 的发病机制中发挥重要作用。然而，仍不清楚全身免疫反应如何导致局部关节紊乱。RA 动物模型的研究揭示了免疫细胞与关节特异性间充质细胞之间相互作用的重要性。特别是，关节特异性间充质细胞通过促进 Th17 细胞向炎症关节迁移，然后通过稳态增殖增加白介素-17 的产生，促进 Th17 介导的 RA 炎症期的扩增。此外，骨免疫学的最新进展为 RA 中骨破坏期的发病机制提供了新的见解。值得注意的是，Th17 细胞已被证明通过关节特异性间充质细胞增强破骨细胞的分化。因此，CD4+T 细胞和关节中非造血间充质细胞的相互作用在炎症和骨破坏两个阶段的 RA 发病机制中都起着关键作用。关注这种相互作用将有助于更好地理解全身免疫反应导致局部关节紊乱的机制，并为新的治疗策略提供分子基础。
