Emerging role of endosomal toll-like receptors in rheumatoid arthritis.
Emerging role of endosomal toll-like receptors in rheumatoid arthritis.
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DOI：
10.3389/fimmu.2014.00001
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发表时间：
2014
影响因子：
7.3
通讯作者：
Sacre S
中科院分区：
文献类型：
--
作者：
Thwaites R;Chamberlain G;Sacre S
Toll 样受体 (TLR) 及其下游信号通路在先天免疫中已得到全面表征。除了这一功能外，这些受体还被认为参与许多自身免疫性疾病的发病机制，包括类风湿性关节炎（RA）。 RA 的小鼠体内模型和人类体外组织模型提供了有关 TLR 和下游信号通路成分的潜在活性的大量信息。虽然大多数早期工作研究细胞表面 TLR，但最近的重点已转移到内体 TLR 3、7、8 和 9。这些受体识别自身和外源双链 RNA 以及单链 RNA 和 DNA。抑制内体 TLR 或其信号级联成分的治疗方法的开发可能代表了一种针对细胞因子产生上游炎症的方法。这可能比包括细胞因子阻断在内的现有疗法具有更高的特异性。在这里，我们回顾了当前的信息，表明内体 TLR 在 RA 发病机制中的作用以及针对这些受体进行治疗的努力。
Toll-like receptors (TLRs) and their downstream signaling pathways have been comprehensively characterized in innate immunity. In addition to this function, these receptors have also been suggested to be involved in the pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA). Murine in vivo models and human in vitro tissue models of RA have provided a wealth of information on the potential activity of TLRs and components of the downstream signaling pathways. Whilst most early work investigated the cell surface TLRs, more recently the focus has moved to the endosomal TLRs 3, 7, 8, and 9. These receptors recognize self and foreign double-stranded RNA and single-stranded RNA and DNA. The development of therapeutics to inhibit the endosomal TLRs or components of their signaling cascades may represent a way to target inflammation upstream of cytokine production. This may allow for greater specificity than existing therapies including cytokine blockade. Here, we review the current information suggesting a role for the endosomal TLRs in RA pathogenesis and the efforts to target these receptors therapeutically.