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Toll-Like Receptor Signaling: Emerging Opportunities in Human Diseases and Medicine

机译:类似收费的信号传导:人类疾病和医学中的新兴机会

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The family of Toll-like receptors (TLR1-TLR11) provides host defense in mammals by inducing proinflammatory innate immune response upon recognition of conserved structural component in pathogens. TLR mediated activation of signaling pathways that induce the expression of proinflammatory molecules is one of the well-studied but ever expanding fields of immunology. As a result, a wealth of information has been obtained which includes the identification of specific ligands of individual TLR, elucidation of their downstream signaling pathways, function of different adaptor proteins, activation of protein kinases and transcription factors that transcribe the genes for inflammatory molecules. TLRs not only sense microbial invasion but also can be activated by endogenous molecules as well as low molecular weight synthetic compounds. Given the role of innate immune machinery to provoke inflammation in host, TLRs signaling may be involved in many acute and chronic inflammatory processes in sterile and post-infection conditions such as, atherosclerosis, leprosy, inflammatory bowel syndrome (IBD), lung airway hyperactivity in allergic asthma, and in sepsis. By the same token, TLRs can also be associated with autoimmune diseases such as systemic lupus erythematosus (SLE) or other immune unresponsive diseases like cancer. In addition, synthetic organic compounds which enhance the function of TLRs can also be useful as potential adjutants to improve conventional vaccination strategy. Here we summarize the recent development on possible modulation of the TLR signaling pathway for therapeutic solution of multiple immune-related diseases.
机译:Toll样受体家族(TLR1-TLR11)通过在识别病原体中保守的结构成分后诱导促炎性先天免疫应答,从而为哺乳动物提供宿主防御。 TLR介导的诱导促炎分子表达的信号传导途径的激活是免疫学领域中经​​过深入研究但仍在不断扩展的领域之一。结果,已经获得了大量信息,包括鉴定单个TLR的特异性配体,阐明其下游信号传导途径,不同衔接子蛋白的功能,蛋白激酶的活化以及转录炎性分子基因的转录因子。 TLR不仅可以感知微生物的入侵,还可以被内源性分子以及低分子量的合成化合物激活。考虑到先天免疫机制在宿主中引起炎症的作用,TLRs信号可能参与无菌和感染后条件下的许多急性和慢性炎症过程,例如动脉粥样硬化,麻风,炎性肠综合症(IBD),肺气道活动过度过敏性哮喘和败血症。同样,TLR也可能与自身免疫性疾病(例如系统性红斑狼疮(SLE))或其他免疫无反应性疾病(例如癌症)相关。另外,增强TLR功能的合成有机化合物也可用作改善常规疫苗接种策略的潜在佐剂。在这里,我们总结了多种免疫相关疾病的治疗解决方案可能对TLR信号通路进行调节的最新进展。

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