Annexin A1 drives macrophage skewing to accelerate muscle regeneration through AMPK activation

Simon McArthur*, Gaetan Juban, Thomas Gobbetti, Thibaut Desgeorges, Marine Theret, Julien Gondin, Juliana E. Toller-Kawahisa, Chris P. Reutelingsperger, Benedicte Chazaud, Mauro Perretti*, Remi Mounier*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

55 Citations (Web of Science)

Abstract

Understanding the circuits that promote an efficient resolution of inflammation is crucial to deciphering the molecular and cellular processes required to promote tissue repair. Macrophages play a central role in the regulation of inflammation, resolution, and repair/regeneration. Using a model of skeletal muscle injury and repair, herein we identified annexin A1 (AnxA1) as the extracellular trigger of macrophage skewing toward a pro-reparative phenotype. Brought into the injured tissue initially by migrated neutrophils, and then overexpressed in infiltrating macrophages, AnxA1 activated FPR2/ALX receptors and the downstream AMPK signaling cascade, leading to macrophage skewing, dampening of inflammation, and regeneration of muscle fibers. Mice lacking AnxA1 in all cells or only in myeloid cells displayed a defect in this reparative process. In vitro experiments recapitulated these properties, with AMPK-null macrophages lacking AnxA1-mediated polarization. Collectively, these data identified the AnxA1/FPR2/AMPK axis as an important pathway in skeletal muscle injury regeneration.

Original languageEnglish
Pages (from-to)1156-1167
Number of pages12
JournalJournal of Clinical Investigation
Volume130
Issue number3
DOIs
Publication statusPublished - 2 Mar 2020

Keywords

  • APOPTOTIC NEUTROPHILS
  • CELL SIZE
  • RESOLUTION
  • INFLAMMATION
  • POLARIZATION
  • MONOCYTES
  • IMMUNOMETABOLISM
  • GLUCOCORTICOIDS
  • AMPK-ALPHA-1
  • PHAGOCYTOSIS

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