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Regulation of muscle growth and regeneration by the immune system
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Journal Article
Regulation of muscle growth and regeneration by the immune system
2017
Overview
Key Points
Changes in the stages of myogenesis during muscle regeneration following injury coincide with changes in the phenotype and activation state of leukocytes that invade the damaged, regenerating tissue.
Macrophages dominate the inflammatory infiltrate in regenerating muscle, and they are biased towards an M1 phenotype during the early, proliferative stages of muscle regeneration and towards an M2 phenotype during the differentiation and growth phase of regeneration.
Signalling initiated by tumour necrosis factor (TNF), interferon-γ (IFNγ), interleukin-10 (IL-10) and insulin-like growth factor 1 (IGF1) has key roles in controlling the normal inflammatory response and myogenic response to muscle damage that is required to achieve muscle regeneration.
Disruptions of normal regulatory interactions between myeloid cells and muscle with regulatory T (T
reg
) cells, CD8
+
T cells and fibro-adipogenic progenitor (FAP) cells can prevent successful muscle regeneration following acute injury.
Chronic muscle disease and muscle ageing disrupt the normal function of myeloid cells, FAP cells and T
reg
cells, which can lead to impaired muscle regeneration and increased muscle fibrosis.
Manipulations of myeloid cell phenotypes can improve muscle regeneration and growth following muscle trauma.
Following muscle injury, changes in the stages of muscle growth coincide with changes in the phenotype and activation status of leukocytes that enter the site of muscle damage. As described in this Review, complex and coordinated crosstalk between immune cells and muscle cells determines the success or failure of muscle regeneration.
Diseases of muscle that are caused by pathological interactions between muscle and the immune system are devastating, but rare. However, muscle injuries that involve trauma and regeneration are fairly common, and inflammation is a clear feature of the regenerative process. Investigations of the inflammatory response to muscle injury have now revealed that the apparently nonspecific inflammatory response to trauma is actually a complex and coordinated interaction between muscle and the immune system that determines the success or failure of tissue regeneration.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
