The complement system has evolved during the past 1.2 billion years, making it one of the oldest parts of the immune system. Since its discovery around 100 years ago, the system has been mainly associated with its role as a first line defense system and guardian of the vascular space. However, several findings published during the past few years suggest that this might be only a small facet of the multiple functions of the system and that we have explored at best the tip of the iceberg.
Recent reports rediscovered complement production within cells, now with a fresh look on activation of complement factors within cells demonstrating novel roles for complement in cell homeostasis, survival and differentiation. The well know mechanisms of canonical pathway activation in response to C1q, MBL or Ficolin sensing, followed by C3 and C5 cleavage through C3 and C5 convertases have been complemented by non-canonical mechanisms, leading to cleavage and activation of complement factors in the circulation and within immune cells. Moreover, it has been shown that the complement system exerts multiple and bidirectional interactions with other sensor and effector systems of innate immunity thereby regulating and controlling responses of both, innate and adaptive immunity. With this plethora of novel functions, playing critical roles in acute and chronic inflammatory diseases, several molecules of the system became attractive therapeutic targets, eventually getting into the spotlight of the pharmaceutical industry.
The July themed issue of the British Journal of Pharmacology highlights in 10 articles recent discoveries that add to the extended view of the complement system with a fresh look on the functions of intracellular complement, thrombosis, trauma, hypertonia, kidney disease and COVID-19.
Canonical and non-canonical functions of the complement system in health and disease, in Wenzel U., Kemper C., Köhl J. (editors). Br. J. Pharmacol. 2021 177 (14) 2749-2907.