Immunobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Trends Immunol. 2013 Jul;34(7):329-35. doi: 10.1016/j.it.2013.03.005. Epub 2013 Apr 20.
We understand much about the agents, receptors, and signalling pathways that lead to immunity to pathogens. Less is known about how the process is initiated in apparently sterile conditions such as spontaneous immunity to certain tumours, tissue grafts, or autoimmune disorders. Proinflammatory molecules released by dying cells, termed damage-associated molecular patterns (DAMPs), have been proposed to activate dendritic cells (DCs) to promote T cell responses to antigens present in cell corpses. Surprisingly, rather than affecting activation, some recently identified DAMP receptors control specialised DC functions such as antigen acquisition and presentation. This selectivity reveals a new point of control in the regulation of adaptive immunity and, potentially, tolerance that renders DAMPs nonredundant players in responses to both sterile and nonsterile insults.
我们对导致病原体免疫的介质、受体和信号通路有了很多了解。但对于在看似无菌的情况下(如对某些肿瘤、组织移植物或自身免疫性疾病的自发免疫),这一过程是如何启动的,我们知之甚少。死亡细胞释放的促炎分子,称为损伤相关分子模式(DAMPs),被认为可以激活树突状细胞(DC),促进 T 细胞对细胞尸体内存在的抗原的反应。令人惊讶的是,最近发现的一些 DAMPs 受体并没有影响激活,而是控制专门的 DC 功能,如抗原摄取和呈递。这种选择性揭示了适应性免疫和潜在的耐受调节中的一个新的控制点,使 DAMPs 在对无菌和非无菌损伤的反应中成为不可或缺的参与者。