TLRs, future potential therapeutic targets for RA.
TLRs, future potential therapeutic targets for RA.
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DOI：
10.1016/j.autrev.2016.12.003
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发表时间：
2017-02
影响因子：
13.6
通讯作者：
Shahrara S
中科院分区：
文献类型：
--
作者：
Elshabrawy HA;Essani AE;Szekanecz Z;Fox DA;Shahrara S
Toll样受体（TLR）在调节先天免疫中具有核心作用，并且在过去十年中研究已经开始揭示它们在增强自身免疫性疾病如类风湿性关节炎（RA）中的重要性。早期的研究强调了TLR 2和TLR 4在RA发病机制中的重要性。在这篇综述中，我们讨论了新的数据表明类风湿关节炎及其临床前模型中的TLR 5和TLR 7的作用。我们评估类风湿关节炎骨髓细胞，滑膜组织成纤维细胞，T细胞，破骨细胞祖细胞和内皮细胞中的TLRs的致病性。这些观察结果表明，TLRs的连接可以将RA骨髓细胞转化为M1巨噬细胞，M1和RA滑膜组织成纤维细胞分泌的炎症因子参与TH-17细胞的发育。从在RA临床前模型中进行的研究，我们得出结论，TLR介导的炎症可以通过互连骨髓和TH-17细胞对关节血管化的反应而导致骨侵蚀。鉴于TLR功能的新的独特方面，我们总结了正在测试的新方法，以损害类风湿关节炎患者的TLR激活。
Toll like receptor (TLR)s have a central role in regulating innate immunity and in the last decade studies have begun to reveal their significance in potentiating autoimmune diseases such as rheumatoid arthritis (RA). Earlier investigations have highlighted the importance of TLR2 and TLR4 function in RA pathogenesis. In this review, we discuss the newer data that indicate roles for TLR5 and TLR7 in RA and its preclinical models. We evaluate the pathogenicity of TLRs in RA myeloid cells, synovial tissue fibroblasts, T cells, osteoclast progenitor cells and endothelial cells. These observations establish that ligation of TLRs can transform RA myeloid cells into M1 macrophages and that the inflammatory factors secreted from M1 and RA synovial tissue fibroblasts participate in TH-17 cell development. From the investigations conducted in RA preclinical models, we conclude that TLR-mediated inflammation can result in osteoclastic bone erosion by interconnecting the myeloid and TH-17 cell response to joint vascularization. In light of emerging unique aspects of TLR function, we summarize the novel approaches that are being tested to impair TLR activation in RA patients.