补体长期以来被视为一种重要的先天免疫效应系统，它介导着宿主防御和组织稳态。然而，越来越多的证据揭示了补体在远超其在先天免疫传统领域之外的基本生物过程中的更广泛参与。补体在细胞外和细胞内空间与多种模式识别和信号通路进行了复杂的串话。除了调节宿主-病原体相互作用外，这种串话还指导早期发育过程和不同细胞轨迹，塑造了不同生理系统中的组织免疫代谢和再生方案。本综述提供了关于补体系统功能的指南。它突出了在进化、中枢神经系统发育、组织再生和癌症免疫等方面重塑了我们对补体病理生物学理解的示范性范式转变的例子。尽管补体激活受到严格的时空调节，但它可能被偏离规范，加剧了炎症组织病理的发生。补体对疾病病理生理学的普遍贡献激发了补体治疗学的复苏，其中一些已经挑战了长期以来的信条。因此，我们重点介绍了临床补体干预的主要治疗概念和里程碑。© 2023. Springer Nature Limited.

Complement has long been considered a key innate immune effector system that mediates host defence and tissue homeostasis. Yet, growing evidence has illuminated a broader involvement of complement in fundamental biological processes extending far beyond its traditional realm in innate immunity. Complement engages in intricate crosstalk with multiple pattern-recognition and signalling pathways both in the extracellular and intracellular space. Besides modulating host-pathogen interactions, this crosstalk guides early developmental processes and distinct cell trajectories, shaping tissue immunometabolic and regenerative programmes in different physiological systems. This Review provides a guide to the system-wide functions of complement. It highlights illustrative paradigm shifts that have reshaped our understanding of complement pathobiology, drawing examples from evolution, development of the central nervous system, tissue regeneration and cancer immunity. Despite its tight spatiotemporal regulation, complement activation can be derailed, fuelling inflammatory tissue pathology. The pervasive contribution of complement to disease pathophysiology has inspired a resurgence of complement therapeutics with major clinical developments, some of which have challenged long-held dogmas. We thus highlight major therapeutic concepts and milestones in clinical complement intervention.© 2023. Springer Nature Limited.