Inflammation and Skeletal Muscle Regeneration: Leave It to the Macrophages

• Published in: Trends in immunology Vol. 41; no. 6; pp. 481 - 492
• Main Author: Chazaud, Bénédicte
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2020; Elsevier Limited; Elsevier
• Subjects: Angiogenesis; Cell differentiation; Chemokines; Crosstalk; Differentiation (biology); efferocytosis; Genotype & phenotype; Humans; Inflammation; Inflammation - immunology; Inflammatory response; Life Sciences; macrophage; Macrophages; Macrophages - immunology; Mesenchyme; Metabolism; Muscle recovery; Muscle, Skeletal - physiology; Muscles; Musculoskeletal system; Myogenesis; Neutrophils; Regeneration; resolution of inflammation; Skeletal muscle; skeletal muscle regeneration; Stem cells; tissue injury; Wound Healing - immunology; inflammatory response; skeletal muscle regeneration; macrophage; tissue injury; resolution of inflammation; efferocytosis
• ISSN: 1471-4906; 1471-4981
• DOI: 10.1016/j.it.2020.04.006

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. Macrophages are key orchestrators of the inflammatory response after tissue injury. They do so by controlling both proinflammatory and restorative/anti-inflammatory phases, and by sequentially exerting a variety of functions impacting on parenchymal, vascular, and fibroblastic cells.The resolution of inflammation is mandatory for tissue repair and consists of shifting the inflammatory status of macrophages from a pro- towards an anti-inflammatory/restorative profile. It is mainly operated by macrophages through efferocytosis, that is, phagocytosis of dead cells and debris.The shift occurring in macrophage inflammatory status and the resolution of inflammation are controlled by integrating early inflammation-resolving cues, efferocytosis, rewiring of cellular metabolism, and activation of specific intracellular signaling pathways.We posit that while the proinflammatory phase is shorter and less intense after tissue injury than during a given infection, this natural response should not be blunted. In injured skeletal muscle, applying an anti-inflammatory treatment too early can be detrimental in returning to homeostasis.