Inflammation is usually considered as harmful; however, it is also necessary for tissue recovery after injury. Macrophages exert immune and nonimmune functions throughout this process. During ...skeletal muscle regeneration, they mount an inflammatory response while exerting trophic roles on muscle and mesenchymal stem cells. Proinflammatory macrophages shift to being anti-inflammatory, triggering the resolution of inflammation. Studies have highlighted that during this shift, a crosstalk ensues, integrating cues for resolution, efferocytosis, cellular metabolism, and signaling pathways. During the restorative phase, macrophages dampen inflammation while promoting stem cell differentiation, angiogenesis, and matrix remodeling. Since blunting the inflammatory phase can be detrimental for muscle regeneration, we suggest that rather than fighting inflammation, it should be allowed to operate and resolve, thus allowing for tissue recovery.
Macrophages are key orchestrators of the inflammatory response after tissue injury. They do so by controlling both proinflammatory and restorative/anti-inflammatory phases, and by sequentially exerting a variety of functions impacting on parenchymal, vascular, and fibroblastic cells.The resolution of inflammation is mandatory for tissue repair and consists of shifting the inflammatory status of macrophages from a pro- towards an anti-inflammatory/restorative profile. It is mainly operated by macrophages through efferocytosis, that is, phagocytosis of dead cells and debris.The shift occurring in macrophage inflammatory status and the resolution of inflammation are controlled by integrating early inflammation-resolving cues, efferocytosis, rewiring of cellular metabolism, and activation of specific intracellular signaling pathways.We posit that while the proinflammatory phase is shorter and less intense after tissue injury than during a given infection, this natural response should not be blunted. In injured skeletal muscle, applying an anti-inflammatory treatment too early can be detrimental in returning to homeostasis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Macrophages, and more broadly inflammation, have been considered for a long time as bad markers of tissue homeostasis. However, if it is indisputable that macrophages are associated with ...many diseases in a deleterious way, new roles have emerged, showing beneficial properties of macrophages during tissue repair and regeneration. This discrepancy is likely due to the high plasticity of macrophages, which may exhibit a wide range of phenotypes and functions depending on their environment. Therefore, regardless of their role in immunity, macrophages play a myriad of roles in the maintenance and recovery of tissue homeostasis. They take a major part in the resolution of inflammation. They also exert various effects of parenchymal cells, including stem and progenitor cell, of which they regulate the fate. In the present review, few examples from various tissues are presented to illustrate that, beyond their specific properties in a given tissue, common features have been described that sustain a role of macrophages in the recovery and maintenance of tissue homeostasis.
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GEOZS, IJS, IMTLJ, KISLJ, NUK, PNG, SAZU, SBCE, SBJE, UL, UPCLJ, UPUK
Increase in the practice of sport by more and more numerous people in the Western countries is associated with an increase in muscle injuries, and in demand for improving muscle function and ...acceleration of muscle recovery after damage. Most of the treatments used target inflammation. Indeed, several lines of experimental evidence in animal models that are supported by human studies identify inflammatory cells, and particularly macrophages, as essential players in skeletal muscle regeneration. Macrophages act not only through their immune functions, but also control myogenesis and extracellular matrix remodeling by directly acting on myogenic precursors and fibro‐adipogenic precursors. In light of these recent biological advances, the question of early treatment aiming at blunting inflammation after exercise‐induced muscle injury is discussed.
The February 2016 issue contains a Special Feature on the Effects of exercise on the immune system and metabolism coming into the Olympic year. The role of the immune system in exercise is complex and challenging. Too little exercise can depress the immune system. In contrast, too much exercise can also lead to a compromised immune system. This is a challenge that athletes face as they prepare for competition. Immunology & Cell Biology thanks the coordinators of this Special Feature ‐ Mark Febbraio and Graeme Lancaster ‐ for their planning and input.
The adult skeletal muscle fully regenerates after injury thanks to the properties of muscle stem cells that follow the adult myogenic program to replace damaged myofibers. Muscle regeneration also ...relies upon the coordinated actions of several other cell types, among which immune cells. Leukocytes infiltrate the damaged muscle soon after injury and support the regeneration process in a variety of ways, from the activation of muscle stem cells to the maturation of newly formed myofibers. Leukocytes also interact with other cell types such as fibroadipogenic precursors and endothelial cells. This review presents the interactions that leukocytes develop with the cells present in their vicinity and the impact they have on skeletal muscle regeneration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Macrophages are highly versatile cells that are involved both in the mounting and the resolution of inflammatory responses. Besides their properties in innate immunity to fight against pathogens, ...macrophages are essential for tissue repair, during which they adopt sequential inflammatory status. While the acquisition of some canonical polarized inflammatory statuses in vitro (M1/M2) is beginning to be understood at the molecular level, the regulation of macrophage skewing in vivo has been less investigated. Immunometabolism, in particular, is an emerging field, and most of the studies so far have investigated the control of macrophage polarization using in vitro set‐ups. In this context, skeletal muscle regeneration is an excellent paradigm to study tissue repair, since the sequential steps of inflammatory response and tissue repair are well characterized. In this Review, after introducing macrophage populations and functions during skeletal muscle regeneration, we present the current knowledge on the metabolic regulation of macrophage inflammatory status, with particular emphasis on the comparison between in vitro and in vivo models of macrophage activation. We also discuss the metabolic regulation of macrophages in vivo during skeletal muscle regeneration.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Adult skeletal muscle regenerates completely after a damage, thanks to the satellite cells, or muscle stem cells (MuSCs), that implement the adult myogenic program. This program is sustained by both ...robust intrinsic mechanisms and extrinsic cues coming from the close neighborhood of MuSCs during muscle regeneration. Among the various cell types present in the regenerating muscle, immune cells, and particularly macrophages, exert numerous functions and provide sequential transient niches to support the myogenic program. The adequate orchestration of the delivery of these cues ensures efficient muscle regeneration and full functional recovery. The situation is very different in muscular dystrophies where asynchronous and permanent microinjuries occur, triggering contradictory regenerating cues at the same time in a specific area, that lead to chronic inflammation and fibrogenesis. Here we review the beneficial effects that leukocytes, and particularly macrophages, exert on their neighboring cells during skeletal muscle regeneration after an acute injury. Then, the more complicated (and less beneficial) roles of leukocytes during muscular dystrophies are presented. Finally, we discuss how the inflammatory compartment may be a target to improve muscle regeneration in both acute muscle injury and muscle diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PURPOSE OF REVIEWThe present review describes the interferon (IFN)-signature currently emerging as a tool for the diagnosis of idiopathic inflammatory myopathies (IIMs), and aims at presenting the ...interests and limitations of this recent tool for the clinics and the research.
RECENT FINDINGSRecent in-vivo and in-vitro transcriptomic studies have evidenced the involvement of IFNs in the pathogenesis of IIMs. A correlation between the IFN-signature and the clinical severity of IIMs has been established. Moreover, studies pointed out differences in the IFN-signature regarding the IIM subgroup (dermatomyositis, polymyositis, inclusion body myositis, anti-synthetase syndrome, immuno-mediated necrotizing myopathies), raising the hypothesis of several pathogenic processes in IIMs.
SUMMARYIIM pathogenesis remains partially understood. IFN-signature represents one of the main recent advances in the field. IFN-signature was identified thanks to transcriptomic analyses of tissues or cells from IIM patients (muscle, skin, blood cells, muscle cells) and should allow to establish new diagnosis and better monitoring of IIM patients. It also provides a tool for investigation of IIM pathogenesis. Nevertheless, IFN-signature still requires accurate definition in order to standardize its use, notably in the clinical practice.
Redox Control of Skeletal Muscle Regeneration Le Moal, Emmeran; Pialoux, Vincent; Juban, Gaëtan ...
Antioxidants & redox signaling,
2017-Aug-10, Volume:
27, Issue:
5
Journal Article
Peer reviewed
Open access
Skeletal muscle shows high plasticity in response to external demand. Moreover, adult skeletal muscle is capable of complete regeneration after injury, due to the properties of muscle stem cells ...(MuSCs), the satellite cells, which follow a tightly regulated myogenic program to generate both new myofibers and new MuSCs for further needs. Although reactive oxygen species (ROS) and reactive nitrogen species (RNS) have long been associated with skeletal muscle physiology, their implication in the cell and molecular processes at work during muscle regeneration is more recent. This review focuses on redox regulation during skeletal muscle regeneration. An overview of the basics of ROS/RNS and antioxidant chemistry and biology occurring in skeletal muscle is first provided. Then, the comprehensive knowledge on redox regulation of MuSCs and their surrounding cell partners (macrophages, endothelial cells) during skeletal muscle regeneration is presented in normal muscle and in specific physiological (exercise-induced muscle damage, aging) and pathological (muscular dystrophies) contexts. Recent advances in the comprehension of these processes has led to the development of therapeutic assays using antioxidant supplementation, which result in inconsistent efficiency, underlying the need for new tools that are aimed at precisely deciphering and targeting ROS networks. This review should provide an overall insight of the redox regulation of skeletal muscle regeneration while highlighting the limits of the use of nonspecific antioxidants to improve muscle function. Antioxid. Redox Signal. 27, 276-310.
Post‐injury skeletal muscle regeneration requires interactions between myogenic and non‐myogenic cells. Our knowledge on the regeneration process is mainly based on models using toxic, chemical, or ...physical (e.g., based on either muscle freezing or crushing) injury. Strikingly, the time course and magnitude of changes in the number of cells involved in muscle regeneration have been poorly described in relation to mild and severe muscle damage induced by electrically‐evoked lengthening contractions. We investigated for the first time the kinetics and magnitude of changes in mononuclear cells in relation to the extent of muscle damage. Mild and severe injury were induced in vivo in the mouse gastrocnemius muscle by 1 and 30 electrically‐evoked lengthening contractions, respectively. Several days after muscle damage, functional analysis of maximal torque production and histological investigations were performed to assess the related cellular changes. Torque recovery was faster after mild injury than after severe muscle damage. More necrotic and regenerating myofibers were observed after severe muscle damage as compared with mild injury, illustrating an association between functional and histological alterations. The kinetics of changes in muscle stem cells (total, proliferating, and differentiating), endothelial cells, fibro‐adipogenic progenitors (FAPs), and macrophages in the regenerating muscle was similar in mild and severe models. However, the magnitude of changes in the number of differentiating muscle stem cells, hematopoietic cells, among which macrophages, and FAPs was higher in severe muscle damage. Collectively, our results show that the amount of myogenic and non‐myogenic cells varies according to the extent of skeletal muscle injury to ensure efficient skeletal muscle regeneration while the kinetics of changes is independent of muscle tissue alterations. The possibility to experimentally modulate the extent of muscle damage will be useful to further investigate the cellular and molecular events involved in muscle regeneration.
The magnitude of changes in mononuclear cells varies in relation to the extent of muscle damage. Severe muscle damage is associated with more numerous differentiating muscle stem cells (MuSCs), hematopoietic cells, among which macrophages (MPs), and fibro‐adipogenic progenitors (FAPs). We also demonstrated that the kinetics of variations in the several cell types (i.e., MuSCs, MPs, FAPs, and endothelial cells ECs) involved in muscle regeneration was similar between mild and severe muscle damage.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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