A guide to complement biology, pathology and therapeutic opportunity.

Autor: Mastellos DC; National Center for Scientific Research 'Demokritos', Athens, Greece., Hajishengallis G; Department of Basic and Translational Sciences, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA., Lambris JD; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. lambris@pennmedicine.upenn.edu.
Jazyk: angličtina
Zdroj: Nature reviews. Immunology [Nat Rev Immunol] 2024 Feb; Vol. 24 (2), pp. 118-141. Date of Electronic Publication: 2023 Sep 05.
DOI: 10.1038/s41577-023-00926-1
Abstrakt: 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.)
Databáze: MEDLINE
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