From Innate to Adaptive Immune Response in Muscular Dystrophies and Skeletal Muscle Regeneration: The Role of Lymphocytes

Figure 1

The complexity of the inflammatory milieu in muscle repair. During the initial phases of muscle damage, degenerating fibers release chemokines and cytokines recruiting mast cells, neutrophils (NEUT), and CD8/CD4 T cells which sustain proinflammatory M1 phenotype of recruited monocytes, thus promoting muscle fibers necrosis and debris clearing. These events are primarily mediated by IL-6, NO, TNFα, and IL-1β release. On the other hand, eosinophils are also recruited, which induce FAPs to sustain MuSCs proliferation via IL-4 release. Eosinophils-induced FAPs-produced follistatin promotes MuSCs differentiation, together with the clonally expanding mTreg which produce Areg. Areg also sustains MuSC proliferation and maintains/induces M2 anti-inflammatory/prohealing phenotype, supporting resolution of inflammation. Unbalance in the kinetics, quality, and activity of any of these actors would prevent resolution of inflammation, making muscle environment unfavourable for muscle regeneration, as it occurs in muscular dystrophies.