The critical role of toll-like receptors--From microbial recognition to autoimmunity: A comprehensive review.
The critical role of toll-like receptors--From microbial recognition to autoimmunity: A comprehensive review.
复制标题
DOI：
10.1016/j.autrev.2015.08.009
复制
发表时间：
2016-01
影响因子：
13.6
通讯作者：
Adamopoulos IE
中科院分区：
文献类型：
--
作者：
Jiménez-Dalmaroni MJ;Gerswhin ME;Adamopoulos IE
Toll样受体（TLR）是天然免疫细胞（包括单核细胞、巨噬细胞和树突状细胞）活化的重要机制。TLR激活巨噬细胞是启动促炎细胞因子TNF、IL-1β和IL-6快速表达的关键，同时促进Th 17应答，所有这些在自身免疫中起关键作用。令人惊讶的是，在炎性关节炎中，特异性TLR的激活不仅可以诱导而且可以抑制与骨破坏相关的细胞过程。来自不同TLR、其内源性或微生物配体和辅助分子的信号的细胞间和细胞内协调决定激活或抑制应答。在此，我们回顾了TLR介导的先天免疫细胞活化和分化为破骨细胞的能力，这些信号有助于关节炎中的骨破坏。详细了解TLR在诱导和抑制关节炎细胞过程中的相反机制可能为开发治疗自身免疫的新疗法铺平道路。
Toll-like receptors (TLRs) constitute an important mechanism in the activation of innate immune cells including monocytes, macrophages and dendritic cells. Macrophage activation by TLRs is pivotal in the initiation of the rapid expression of pro-inflammatory cytokines TNF, IL-1β and IL-6 whilst promoting Th17 responses, all of which play critical roles in autoimmunity. Surprisingly, in inflammatory arthritis, activation of specific TLRs can not only induce but also inhibit cellular processes associated with bone destruction. The intercellular and intracellular orchestration of signals from different TLRs, their endogenous or microbial ligands and accessory molecules determines the activating or inhibitory responses. Herein, we review the TLR-mediated activation of innate immune cells in their activation and differentiation to osteoclasts and the capacity of these signals to contribute to bone destruction in arthritis. Detailed understanding of the opposing mechanisms of TLRs in the induction and suppression of cellular processes in arthritis may pave the way to develop novel therapies to treat autoimmunity.