AMPKα1 Regulates Macrophage Skewing at the Time of Resolution of Inflammation during Skeletal Muscle Regeneration.: AMPKα1 regulates macrophage skewing

Rémi Mounier 1 Marine Théret 1 Ludovic Arnold 2 Sylvain Cuvellier 1 Laurent Bultot 3 Olga Göransson 4 Nieves Sanz 1 Arnaud Ferry 5 Kei Sakamoto 3 Marc Foretz 1 Benoit Viollet 1 Bénédicte Chazaud 1, *
* Corresponding author
1 IC UM3 (UMR 8104 / U1016) - Institut Cochin
2 Immunité et Infection
3 Nestlé Institute of Health Sciences SA [Lausanne, Switzerland]
4 Department of Experimental Medical Sciences [Lund, Sweden]
5 Institut de Myologie
Abstract : Macrophages control the resolution of inflammation through the transition from a proinflammatory (M1) to an anti-inflammatory (M2) phenotype. Here, we present evidence for a role of AMPKα1, a master regulator of energy homeostasis, in macrophage skewing that occurs during skeletal muscle regeneration. Muscle regeneration was impaired in AMPKα1(-/-) mice. In vivo loss-of-function (LysM-Cre;AMPKα1(fl/fl) mouse) and rescue (bone marrow transplantation) experiments showed that macrophagic AMPKα1 was required for muscle regeneration. Cell-based experiments revealed that AMPKα1(-/-) macrophages did not fully acquire the phenotype or the functions of M2 cells. In vivo, AMPKα1(-/-) leukocytes did not acquire the expression of M2 markers during muscle regeneration. Skewing from M1 toward M2 phenotype upon phagocytosis of necrotic and apoptotic cells was impaired in AMPKα1(-/-) macrophages and when AMPK activation was prevented by the inhibition of its upstream activator, CaMKKβ. In conclusion, AMPKα1 is crucial for phagocytosis-induced macrophage skewing from a pro- to anti-inflammatory phenotype at the time of resolution of inflammation.
Keywords : skeletal muscle regeneration AMPK Macrophage phagocytosis resolution of inflammation
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Rémi Mounier, Marine Théret, Ludovic Arnold, Sylvain Cuvellier, Laurent Bultot, et al.. AMPKα1 Regulates Macrophage Skewing at the Time of Resolution of Inflammation during Skeletal Muscle Regeneration.: AMPKα1 regulates macrophage skewing. Cell Metab, 2013, 18 (2), pp.251-64. ⟨10.1016/j.cmet.2013.06.017⟩. ⟨inserm-00857933v2⟩

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