Inflammation and Skeletal Muscle Regeneration: Leave It to the Macrophages!

Inflammation is usually considered as harmful; however, it is also necessary for tissue recovery after injury. Macrophages exert immune and nonimmune functions throughout this process. During skeletal muscle regeneration, they mount an inflammatory response while exerting trophic roles on muscle and mesenchymal stem cells. Proinflammatory macrophages shift to being anti-inflammatory, triggering the resolution of inflammation. Studies have highlighted that during this shift, a crosstalk ensues, integrating cues for resolution, efferocytosis, cellular metabolism, and signaling pathways. During the restorative phase, macrophages dampen inflammation while promoting stem cell differentiation, angiogenesis, and matrix remodeling. Since blunting the inflammatory phase can be detrimental for muscle regeneration, we suggest that rather than fighting inflammation, it should be allowed to operate and resolve, thus allowing for tissue recovery.