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Article Dans Une Revue Journal of Clinical Investigation Année : 2020

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

Simon Mcarthur
  • Fonction : Auteur
Gaëtan Juban
Thomas Gobbetti
  • Fonction : Auteur
Thibaut Desgeorges
  • Fonction : Auteur
Marine Theret
Julien Gondin
Juliana E Toller-Kawahisa
  • Fonction : Auteur
Chris P Reutelingsperger
  • Fonction : Auteur
Bénédicte Chazaud
Mauro Perretti
  • Fonction : Auteur
Rémi Mounier

Résumé

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 proreparative 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.
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Dates et versions

hal-03043169 , version 1 (07-12-2020)

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Simon Mcarthur, Gaëtan Juban, Thomas Gobbetti, Thibaut Desgeorges, Marine Theret, et al.. Annexin A1 drives macrophage skewing to accelerate muscle regeneration through AMPK activation. Journal of Clinical Investigation, 2020, 130, pp.1156 - 1167. ⟨10.1172/jci124635⟩. ⟨hal-03043169⟩
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