Complement: The Road Less Traveled

Claudia Kemper, Viviana P. Ferreira, Jeanne T. Paz, V. Michael Holers, Michail S. Lionakis, Jessy J. Alexander*

*Corresponding author for this work
5 Citations (Scopus)


The complement field has recently experienced a strong resurgence of interest because of the unexpected discovery of new complement functions extending complement’s role beyond immunity and pathogen clearance, a growing list of diseases in which complement plays a role, and the proliferation of complement therapeutics. Importantly, although the majority of complement components in the circulation are generated by the liver and activated extracellularly, complement activation unexpectedly also occurs intracellularly across a broad range of cells. Such cell-autonomous complement activation can engage intracellular complement receptors, which then drive noncanonical cell-specific effector functions. Thus, much remains to be discovered about complement biology. In this brief review, we focus on novel noncanonical activities of complement in its “classic areas of operation” (kidney and brain biology, infection, and autoimmunity), with an outlook on the next generation of complement-targeted therapeutics.

Original languageEnglish
JournalJournal of Immunology
Issue number2
Pages (from-to)119-225
Number of pages107
Publication statusPublished - 15.01.2023

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

DFG Research Classification Scheme

  • 204-05 Immunology

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