TLR2、TLR4与类风湿关节炎

Toll样受体（TLRs）是天然免疫系统中特异性的Ⅰ型跨膜受体及病原模式识别受体，在急性炎症反应、细胞信号转导和细胞凋亡中起重要作用。TLRs通过选择性的识别病原体中病原相关分子模式的保守结构及某些内源性配体，触发髓样细胞分化因子88（MyD88）依赖性和非依赖性途径，导致基因编码的的促炎性细胞因子和趋化因子的激活，从而诱发局部的炎症，并通过上调抗原递呈细胞表面的共刺激分子，诱导T、B淋巴细胞分化，激动后继的适应性免疫应答。类风湿关节炎（RA ）主要表现为滑膜组织炎性增生和炎症细胞浸润最终导致组织破坏和功能障碍。与T细胞过度活化以及B细胞的过度刺激致大量自身抗体产生有关。研究发现，细胞表面的TLRs，尤其是TLR2和TLR4，在类风湿关节炎疾病的发生发展中起重要作用。该文就TLR2、TLR4在RA发病中的作用作一综述，旨在为后期药物干预提供一定的理论依据。

TLR2 and TLR4 in Rheumatoid arthritis

Toll like receptors(TLRs)are pattern recognition receptors belonging to innate immunity and the typeⅠtransmenbrane glyco-protein receptor family that play an essential role in inflammation,cells signal transduction and apoptosis.Besides these exogenous pathogen-associated molecular patterns,TLRs can also bind with these endogenous ligands.By combine with their ligands,extracelluar signals enter into cell and activate the trigger the Myeloid differentiation factor 88 (MyD88 )in dependent or independent pathway, cause the activation of inflammatory cytokines and chemokines,lead to the host’s inflammatory response.Besides,the signals can also upregulate the costimulatory molecules on the surfaces of antigen-presenting cells,induce the differentiation of T or B lymphocytes,ex-cite the following adaptive immune response.Rheumatoid arthritis (RA)is a chronic autoimmune disease,characterized by cytokines-mediated inflammation of the synovial lining of joints and destruction of cartilage and bone.It was related with the T cell hyperactivity and B cell overstimulation leading to overproduction of autoantibodies.Study found that TLRs,especially the TLR2 and TLR4,play a critical action in RA.In this review,to provide a theoretical basis for further drug intervention study we summarized the TLR2/4and their function in RA.