School of Biochemistry and Immunology, and Immunology Research Centre, Trinity College Dublin, Ireland.
Curr Opin Pharmacol. 2011 Aug;11(4):404-11. doi: 10.1016/j.coph.2011.03.004. Epub 2011 Apr 16.
Toll-like receptors (TLRs) play a crucial role in innate immune responses to infection. Binding of agonists to TLRs promotes maturation of antigen presenting cells, such as dendritic cells, which in turn directs the induction of adaptive immune responses. For this reason TLR agonists are being exploited as vaccine adjuvants for infectious disease or cancer and as therapeutics against tumors. However TLR agonists also promote inflammatory cytokine production and have a pathogenic role in many diseases with an inflammatory basis, including autoimmune diseases. Consequently, antibodies to TLRs and inhibitors of TLR signalling pathways have considerable potential as therapeutics for inflammatory disorders. Some have shown to be efficacious in pre-clinical models, and have now entered clinical trials.
Toll-like 受体(TLRs)在感染的固有免疫反应中发挥着关键作用。激动剂与 TLRs 的结合促进了抗原呈递细胞(如树突状细胞)的成熟,进而指导适应性免疫反应的诱导。出于这个原因,TLR 激动剂被用作传染病或癌症的疫苗佐剂,以及对抗肿瘤的治疗方法。然而,TLR 激动剂也促进炎症细胞因子的产生,并在许多具有炎症基础的疾病中具有致病性作用,包括自身免疫性疾病。因此,TLR 抗体和 TLR 信号通路抑制剂作为炎症性疾病的治疗方法具有很大的潜力。一些在临床前模型中显示出疗效,现在已经进入临床试验。