Abstract
Skeletal muscle has an extraordinary regenerative capacity reflecting the rapid activation and effective differentiation of muscle stem cells (MuSCs). In the course of muscle regeneration, MuSCs are reprogrammed by immune cells. In turn, MuSCs confer immune cells anti-inflammatory properties to resolve inflammation and facilitate tissue repair. Indeed, MuSCs can exert therapeutic effects on various degenerative and inflammatory disorders based on their immunoregulatory ability, including effects primed by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). At the molecular level, the tryptophan metabolites, kynurenine or kynurenic acid, produced by indoleamine 2,3-dioxygenase (IDO), augment the expression of TNF-stimulated gene 6 (TSG6) through the activation of the aryl hydrocarbon receptor (AHR). In addition, insulin growth factor 2 (IGF2) produced by MuSCs can endow maturing macrophages oxidative phosphorylation (OXPHOS)-dependent anti-inflammatory functions. Herein, we summarize the current understanding of the immunomodulatory characteristics of MuSCs and the issues related to their potential applications in pathological conditions, including COVID-19.
Highlights
Biologists have been puzzled with the near perfect ability to regenerate severed body parts in certain animals
M1 macrophages contribute to a spectrum of proinflammatory cytokines, including, but not limited to, IFN-γ, tumor necrosis factor-α (TNF-α), IL-1β and IL-6, conditioning the immune microenvironment to promote the rapid proliferation of muscle stem cells (MuSCs) and simultaneously restrain the early differentiation steps of MuSCs [48, 52–56]
We identified a novel anti-inflammatory function of MuSCs that is based on their production of insulin growth factor 2 (IGF2)
Summary
Redressing the interactions between stem cells and immune system in tissue regeneration Jiankai Fang1† , Chao Feng1,2†, Wangwang Chen, Pengbo Hou, Zhanhong Liu, Muqiu Zuo, Yuyi Han, Chenchang Xu1, Gerry Melino , Alexei Verkhratsky , Ying Wang5* , Changshun Shao1* and Yufang Shi1,5*
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