Bryant Clare E, Orr Selinda, Ferguson Brian, Symmons Martyn F, Boyle Joseph P, Monie Tom P
Departments of Veterinary Medicine (C.E.B., J.P.B., T.P.M.), Pathology (B.F.), and Biochemistry (M.F.S., J.P.B.), University of Cambridge, Cambridge, United Kingdom; and Institute of Infection and Immunity, Cardiff University, Cardiff, United Kingdom (S.O.)
Departments of Veterinary Medicine (C.E.B., J.P.B., T.P.M.), Pathology (B.F.), and Biochemistry (M.F.S., J.P.B.), University of Cambridge, Cambridge, United Kingdom; and Institute of Infection and Immunity, Cardiff University, Cardiff, United Kingdom (S.O.).
Pharmacol Rev. 2015;67(2):462-504. doi: 10.1124/pr.114.009928.
Since the discovery of Toll, in the fruit fly Drosophila melanogaster, as the first described pattern recognition receptor (PRR) in 1996, many families of these receptors have been discovered and characterized. PRRs play critically important roles in pathogen recognition to initiate innate immune responses that ultimately link to the generation of adaptive immunity. Activation of PRRs leads to the induction of immune and inflammatory genes, including proinflammatory cytokines and chemokines. It is increasingly clear that many PRRs are linked to a range of inflammatory, infectious, immune, and chronic degenerative diseases. Several drugs to modulate PRR activity are already in clinical trials and many more are likely to appear in the near future. Here, we review the different families of mammalian PRRs, the ligands they recognize, the mechanisms of activation, their role in disease, and the potential of targeting these proteins to develop the anti-inflammatory therapeutics of the future.
自1996年在果蝇黑腹果蝇中发现Toll作为首个被描述的模式识别受体（PRR）以来，已经发现并鉴定了许多这类受体家族。PRR在病原体识别中发挥着至关重要的作用，以启动最终与适应性免疫产生相关的先天性免疫反应。PRR的激活导致免疫和炎症基因的诱导，包括促炎细胞因子和趋化因子。越来越清楚的是，许多PRR与一系列炎症、感染、免疫和慢性退行性疾病有关。几种调节PRR活性的药物已经在进行临床试验，并且在不久的将来可能会出现更多药物。在这里，我们综述了哺乳动物PRR的不同家族、它们识别的配体、激活机制、它们在疾病中的作用以及靶向这些蛋白质以开发未来抗炎疗法的潜力。
