biostudies-literatureCaratti GDeutscher Akademischer AustauschdienstCentre National de la Recherche ScientifiqueInstitut National de la Santé et de la Recherche MédicaleFondation pour la Recherche Médicalee55363https://www.ebi.ac.uk/biostudies/studies/S-EPMC9900347biostudies-literatureUnknown24(2)Macrophages are key cells after tissue damage since they mediate both acute inflammatory phase and regenerative inflammation by shifting from pro-inflammatory to restorative cells. Glucocorticoids (GCs) are the most potent anti-inflammatory hormone in clinical use, still their actions on macrophages are not fully understood. We show that the metabolic sensor AMP-activated protein kinase (AMPK) is required for GCs to induce restorative macrophages. GC Dexamethasone activates AMPK in macrophages and GC receptor (GR) phosphorylation is decreased in AMPK-deficient macrophages. Loss of AMPK in macrophages abrogates the GC-induced acquisition of their repair phenotype and impairs GC-induced resolution of inflammation in vivo during post-injury muscle regeneration and acute lung injury. MechanistEMBO reportsMacrophagic AMPKα1 orchestrates regenerative inflammation induced by glucocorticoids.PMC9900347DEQ20140329495Mounier RKoenen MCaratti GStifel UFessard ATheret MDesgeorges TSkurk CChazaud BTuckermann JPJuban GCaratti BfalseMacrophagic AMPKα1 orchestrates regenerative inflammation induced by glucocorticoids.Macrophages are key cells after tissue damage since they mediate both acute inflammatory phase and regenerative inflammation by shifting from pro-inflammatory to restorative cells. Glucocorticoids (GCs) are the most potent anti-inflammatory hormone in clinical use, still their actions on macrophages are not fully understood. We show that the metabolic sensor AMP-activated protein kinase (AMPK) is required for GCs to induce restorative macrophages. GC Dexamethasone activates AMPK in macrophages and GC receptor (GR) phosphorylation is decreased in AMPK-deficient macrophages. Loss of AMPK in macrophages abrogates the GC-induced acquisition of their repair phenotype and impairs GC-induced resolution of inflammation in vivo during post-injury muscle regeneration and acute lung injury. Mechanist2023-01-01T00:00:00Z2023 Feb2025-05-29T22:09:08.519Z2024-11-09T08:44:19.007ZS-EPMC99003473652037210.15252/embr.202255363