Transcriptional control of macrophage inflammatory shift during skeletal muscle regeneration

Skeletal muscle is a tissue able to fully regenerate after an acute injury. Macrophages play an essential role during skeletal muscle regeneration. Resolution of inflammation is a crucial step during the regeneration process, allowing to contain the inflammatory response to avoid damage of the healthy surrounding muscle and triggers the recovery phase during which the muscle regenerates. Resolution of inflammation is mainly mediated by macrophage phenotypic shift that is the transition from a pro-inflammatory damage associated profile towards an anti-inflammatory restorative phenotype, which is characterized by a major transcriptional rewiring. Failure of the resolution of inflammation is observed in chronic diseases such as degenerative myopathies where permanent asynchronous muscle injuries trigger contradictory inflammatory cues, leading to fibrosis and alteration of muscle function. This review will focus on the described molecular pathways that control macrophage inflammatory shift during skeletal muscle regeneration. First, we will highlight the transcriptional changes that characterize macrophage inflammatory shift during skeletal muscle regeneration. Then, we will describe how the signaling pathways and the metabolic changes associated with this shift are controlled. Finally, we will emphasize the transcription factors involved.