Afzali Behdad, Singh Parul, Tajmul Md, Kemper Claudia
Immunoregulation Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, Md.
Complement and Inflammation Research Section, National Heart, Lung, and Blood Institute, NIH, Bethesda, Md.
J Allergy Clin Immunol. 2025 Aug;156(2):215-223. doi: 10.1016/j.jaci.2025.03.024. Epub 2025 Apr 5.
Our understanding of the complement system continues to grow beyond that of a liver-derived systemically operative mechanism of pathogen clearance to a central orchestrator of single-cell behavior and tissue biology. These expanded activities reflect the extrahepatic and local production of complement by many, if not most, cells, and the unexpected recent finding that complement also serves important physiological intracellular roles. The complement core component C3 has emerged as a particularly critical player in basic cell functions. Here, we provide an overview of the currently known forms and functions of intracellular C3 and the mechanisms that control it. We also discuss 2 emerging concepts as potential key areas for future exploration: intracellular C3 as a second layer of pathogen defense at host-environmental interfaces and "C3 licensing." We conclude by suggesting that the potential clinical implications surrounding perturbations in intracellular C3 activities should be explored better.
我们对补体系统的理解不断拓展，已从一种源自肝脏的系统性病原体清除机制，发展成为单细胞行为和组织生物学的核心协调者。这些扩展的活动反映了许多（即便不是大多数）细胞在肝外和局部产生补体，以及最近意外发现补体在细胞内也发挥着重要的生理作用。补体核心成分C3已成为基础细胞功能中特别关键的参与者。在此，我们概述了细胞内C3目前已知的形式和功能以及控制它的机制。我们还讨论了两个新兴概念，作为未来探索的潜在关键领域：细胞内C3作为宿主 - 环境界面病原体防御的第二层防线以及“C3许可”。我们最后建议，应更好地探索细胞内C3活性扰动周围潜在的临床意义。
