Innate immunity and skeletal muscle repair and homeostasis – Myo-repair

Muscle tissue repair is a most complex biological process that prominently involves activation of myogenic stem cell/progenitors, called satellite cells (SCs), that reside beneath the basal lamina of muscle fibersWe established that, in muscle, quiescent sub-laminal SCs are stably located close to muscle capillaries, and vary in number proportionally to capillarization.This anatomical characteristic is strategic since SC progeny specifically interact with endothelial cells to spatio-temporally coordinate angio-myogenesis and allow growing myofibers to benefit from an appropriately enhanced blood supply.We also established that a maturation compartment transiently exists in injured skeletal muscle, involves macrophages (MPs), and is set up by progenitors themselves. Lability of this compartment in muscle is adapted to discontinuous needs.MP supportive cues include delivery of both mitogenic signals to myoblasts, involving sequencial release of soluble factors , and contact-mediated pro-survival signals to myotubes, involving a set of cell adhesion systems.The present project aims at further investigating the non-stem cell role of innate immune cells in skeletal muscle repair and homeostasis on the grounds of both recent advances in MP biology, and results driven by original myopathologic observations: - Part I will evaluate monocyte subsets and MP states of activation involved in muscle tissue repair - Part 2 will evaluate the role of resident MPs at early and late stages of acute muscle regeneration - Part 3 will evaluate MP-fibroblasts interactions at work in myoinflammation and fibrosis. ...