The complement receptor C5AR2: A powerful modulator of innate and adaptive immunity

Xaria X. Li, John D. Lee, Claudia Kemper, Trent M. Woodruff*

*Corresponding author for this work


Complement activation generates the core effector protein C5a, a potent immune molecule that is linked to multiple inflammatory diseases. Two C5a receptors, C5aR1 (C5aR, CD88) and C5aR2 (C5L2, GPR77), mediate the biological activities of C5a. Although C5aR1 has broadly acknowledged proinflammatory roles, C5aR2 remains at the center of controversy, with existing findings supporting both immune-activating and immune-dampening functions. Recent progress has been made toward resolving these issues. Instead of being a pure recycler and sequester of C5a, C5aR2 is capable of mediating its own set of signaling events and through these events exerting significant immunomodulatory effects not only toward C5aR1 but also other pattern recognition receptors and innate immune systems, such as NLRP3 inflammasomes. This review highlights the existing knowns and unknowns concerning C5aR2 and provides a timely update on recent breakthroughs which are expected to have a substantial impact on future fundamental and translational C5aR2 research.

Original languageEnglish
JournalJournal of Immunology
Issue number12
Pages (from-to)3339-3348
Number of pages10
Publication statusPublished - 15.06.2019

Research Areas and Centers

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


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