Fig. 1

The reciprocal interaction between MuSCs and immune cells during muscle regeneration. Trauma to muscle evokes dramatic immune challenge. Within hours, damaged muscle tissue experiences mast cell degranulation, invasion by neutrophils, infiltration by M1 macrophages, and trafficking of effector T cells. These immune cells condition the inflammatory environment that is enriched with pro­inflammatory cytokines, including IFN-γ and TNF-α, and direct rapid expansion of the MuSC population. The shift of macrophage phenotype functionally couples with the transition of stages of myogenesis. IGF1 modulates autocrine polarization of pro-inflammatory macrophages towards a M2 phenotype. Treg cells also promote the transition of macrophage phenotype through paracrine action of IL-10. Furthermore, MuSCs could orchestrate inflammatory microenvironments through directing the switch towards anti-inflammatory macrophages via the action of IGF2. The resolution of inflammation through multiple mechanisms drives the later stages of MuSC differentiation. Thus, the bidirectional interaction between MuSCs and immune cells determines the course and outcome of muscle regeneration