p38/MKP-1–regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair

Macrophages: Supportive cells for tissue repair and regeneration

“…Then M2 cells appear rapidly, expressing higher amounts of IL-10 and TGFβ and these cells predominate during several days. At the end of muscle regeneration, not only the number of macrophages decreases but the phenotype of both Ly6C pos F4/80 pos (F4/80 is a macrophagic marker) and LY6C neg F4/80 pos cells changes towards a dampening of all cytokine markers, suggesting a skewing into M2 resolving/silencing macrophages (Perdiguero et al, 2011). Very importantly, perturbing this kinetics strongly alters muscle regeneration.…”

“…Indeed, a too early anti-inflammatory signal (e.g. injection of IL-10 or blocking IFNγ few days after injury) as well as blocking later anti-inflammatory signals (injection of anti-IL-10 antibodies during the last phase of muscle regeneration) impedes muscle regeneration (Cheng et al, 2008;Perdiguero et al, 2011).…”

Muscle stem cell aging: regulation and rejuvenation

“…However, whether dysregulated and persistent inflammation has a direct or indirect role in age-associated satellite cell dysfunction is a question that remains to be investigated. Nevertheless, given the shared inflammatory pathogenesis across age-associated diseases [1] and the role of inflammation in satellite cell function and muscle regeneration [70][71][72][73], it is likely that the satellite cell aging process contains an inflammatory component.…”

Macrophages decide between regeneration and fibrosis in muscle

“…Reciprocally, pharmacological inhibition of TGFb1 receptor increased the FAP apoptotic rate thus decreasing FAP numbers. Interestingly, a similar timely crosstalk between TNF and IL-10 (another proregenerative cytokine) in muscle repair has been previously suggested [7]. Whether IL-10 also regulates FAPs survival and fibrogenic activities remains to be investigated.…”

“…In skeletal muscle, proinflammatory macrophages accumulate first in the injured tissue area to phagocytose debris and stimulate satellite cell proliferation, subsequently converting to anti-inflammatory macrophages (or proregenerative macrophages) that support formation and growth of new myofibers [6]. The importance of maintaining the timely balance of proper cell types, soluble growth factors and cytokines in the regenerative microenvironment is highlighted by the fact that forced disruption of macrophage polarization leads to impaired regeneration, caused by dysregulation of satellite cell and vessel-associated cell functions [7][8][9]. Whether these critical immune cells also dialogue with the FAPs during the regenerative process was not known.…”