Inflammation and bone destruction in arthritis: synergistic activity of immune and mesenchymal cells in joints.
Inflammation and bone destruction in arthritis: synergistic activity of immune and mesenchymal cells in joints.
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DOI：
10.3389/fimmu.2012.00077
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发表时间：
2012
影响因子：
7.3
通讯作者：
Takayanagi H
中科院分区：
文献类型：
--
作者：
Komatsu N;Takayanagi H
类风湿性关节炎（RA）是一种免疫介导的关节疾病，其特征是慢性炎症和滑膜增生，最终导致软骨和骨破坏。滑膜成纤维细胞是一种间充质细胞，由于其在炎症环境中的超增殖和超敏感特性以及炎症细胞因子和基质降解酶的大量产生，被认为是RA的关键细胞群。在免疫细胞方面，大量证据表明，CD4+T细胞，特别是产生IL-17的辅助性T （Th17）细胞，在RA的全身免疫反应的启动中起着突出的作用。然而，目前尚不清楚关节局部慢性炎症是如何由全身免疫反应引起的。最近的研究揭示了关节中免疫细胞和间充质细胞之间相互作用的重要性，包括滑膜成纤维细胞。特别是，间充质细胞通过促进Th17细胞向炎症部位的迁移，然后稳态增殖和伴随的IL-17产生的增加，参与了RA中Th17介导的慢性炎症。此外，骨免疫学的最新进展为RA中发生的骨破坏的发病机制提供了新的见解。th17相关的细胞因子已被证明可以促进破骨细胞的形成，主要是通过滑膜成纤维细胞。因此，间充质细胞是连接全身免疫反应和关节局部疾病的RA发展的决定因素。此外，免疫细胞和间充质细胞的相互作用在风湿性关节炎的慢性炎症和骨破坏中起着关键作用。阐明这种相互作用中涉及的精确事件将有助于更好地理解由全身免疫反应引起的关节慢性炎症和骨破坏的机制，也将有助于为治疗类风湿性关节炎的新治疗策略提供分子基础。
Rheumatoid arthritis (RA) is an immune-mediated disease of the joints that is characterized by chronic inflammation and synovial hyperplasia that eventually lead to cartilage and bone destruction. Synovial fibroblasts are mesenchymal cells recognized as a key cell population in RA due to their hyperproliferative and hypersensitive properties in the inflammatory milieu and hyperproduction of both inflammatory cytokines and matrix-degrading enzymes. On the immune cell side, a wealth of evidence has shown that CD4+T-cells, especially IL-17 producing helper T (Th17) cells, play a prominent role, particularly in the initiation of systemic immune response in RA. However, it is still unclear how the local chronic inflammation in the joint is elicited by a systemic immune response. Recent studies have shed light on the importance of the interaction between immune and mesenchymal cells in joints including synovial fibroblasts. In particular, mesenchymal cells contribute to the Th17-mediated chronic inflammation in RA by promoting the migration of Th17 cells to the inflamed site and then the homeostatic proliferation and concomitant increase in IL-17 production. In addition, recent progress in osteoimmunology has provided new insight into the pathogenesis of the bone destruction which takes place in RA. Th17-related cytokines have been shown to enhance osteoclastogenesis, mainly via synovial fibroblasts. Thus, mesenchymal cells are a determinant of the development of RA that links the systemic immune response and the local disorder in the joints. In addition, the interaction of immune and mesenchymal cells plays a key role in both the chronic inflammation and bone destruction seen in RA. Elucidation of the precise events involved in this interaction will lead to a better understanding of the mechanisms by which chronic inflammation and bone destruction in joint results from a systemic immune response, and also will help provide a molecular basis for novel therapeutic strategies to treat RA.
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DOI：
10.1084/jem.191.2.313
发表时间：
2000-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Horai R;Saijo S;Tanioka H;Nakae S;Sudo K;Okahara A;Ikuse T;Asano M;Iwakura Y
通讯作者：
Iwakura Y
影响因子：
56.9
作者：
Asagiri, Masataka;Hirai, Toshitake;Takayanagi, Hiroshi
通讯作者：
Takayanagi, Hiroshi
影响因子：
--
作者：
Cosmi, Lorenzo;Cimaz, Rolando;Annunziato, Francesco
通讯作者：
Annunziato, Francesco
影响因子：
15.9
作者：
Abdollahi-Roodsaz, Shahla;Joosten, Leo A. B.;Van den Berg, Wim B.
通讯作者：
Van den Berg, Wim B.
影响因子：
--
作者：
Fleischmann, Roy;Cutolo, Maurizio;Zwillich, Samuel H.
通讯作者：
Zwillich, Samuel H.