Rôle de l’horloge biologique dans le processus inflammatoire durant la régénération du muscle squelettique

Skeletal muscle ensures movement and posture, and is essential for whole-body energy homeostasis. Importantly, this tissue has a remarkable capacity to regenerate following injury, either due to contractions or more severe traumatic lesions common in sport medicine or muscular dystrophies. This regenerative process involves muscle stem cells (MSCs) activation, differentiation and fusion into regenerated fibers. During regeneration, the myogenic process requires also the recruitment of immune cells such as monocytes/macrophages which allows debris clearance and restores tissue homeostasis. Initiation, development and resolution of inflammation is essential for proper skeletal muscle regeneration and a coordinated interaction between MSCs and different inflammatory cells is essential. Innate lymphoid cells (ILCs) are a recently identified subset of leukocytes playing a key role in innate immune response. These cells display critical and non-redundant functions in maintaining tissue homeostasis and respond rapidly to tissue damage. Their role in skeletal muscle regeneration has not been investigated yet. So first, we seek to highlight the role of ILCs in this context. Moreover, several studies suggest that the biological clock is involved in tissue regeneration processes, especially in the circadian control of stem cell biology. In addition, immune cells hold an intrinsic clock and as a consequence various immune functions, such as leucocytes recruitment to tissue or cytokines release, are under circadian variations. Thus, this project also aims at determining the role of the biological clock in the control of the inflammatory process during skeletal muscle regeneration, notably through the study of the nuclear receptor Rev-erbα which is part of core clock machinery.