title: Regulatory T cells and skeletal muscle regeneration.
abstract: Skeletal muscle regeneration results from the activation and differentiation of myogenic stem cells, called satellite cells, located beneath the basal lamina of the muscle fibers. Inflammatory and immune cells have a crucial role in the regeneration process. Acute muscle injury causes an immediate transient wave of neutrophils followed by a more persistent infiltration of M1 (proinflammatory) and M2 (anti-inflammatory/proregenerative) macrophages. New studies show that injured muscle is also infiltrated by a specialized population of regulatory T (Treg) cells, which control both the inflammatory response, by promoting the M1-to-M2 switch, and the activation of satellite cells. Treg cells accumulate in injured muscle in response to specific cytokines, such as IL-33, and promote muscle growth by releasing growth factors, such as amphiregulin. Muscle repair during aging is impaired due to reduced number of Treg cells and can be enhanced by IL-33 supplementation. Migration of Treg cells could also contribute to explain the effect of heterochronic parabiosis, whereby muscle regeneration of aged mice can be improved by a parabiotically linked young partners. In mdx dystrophin-deficient mice, a model of human Duchenne muscular dystrophy, muscle injury, and inflammation is mitigated by expansion of the Treg-cell population but exacerbated by Treg-cell depletion. These findings support the notion that immunological mechanisms are not only essential in the response to pathogenic microbes and tumor cells but also have a wider homeostatic role in tissue repair, and open new perspectives for boosting muscle growth in chronic muscle disease and during aging.
authors.affiliation: Venetian Institute of Molecular Medicine (VIMM), Padova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Schiaffino
authors.affiliation: Venetian Institute of Molecular Medicine (VIMM), Padova, Italy.|Department of Biomedical Sciences, University of Padova, Italy.
authors.forename: Marcelo G
authors.initials: MG
authors.lastname: Pereira
authors.affiliation: Venetian Institute of Molecular Medicine (VIMM), Padova, Italy.|Department of Medicine (DIMED), University of Padova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ciciliot
authors.affiliation: Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milano, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rovere-Querini
mesh_terms: D000375:Aging; D066258:Amphiregulin / Q000235:genetics / Q000276:immunology; D000818:Animals; D002465:Cell Movement; D005786:Gene Expression Regulation; D006801:Humans; D000067596:Interleukin-33 / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D018101:Mice, Inbred mdx; D018485:Muscle Fibers, Skeletal / Q000276:immunology / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D012038:Regeneration / Q000276:immunology*; D032496:Satellite Cells, Skeletal Muscle / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D066258:Amphiregulin; C587849:Areg protein, mouse; C506535:Il33 protein, mouse; D000067596:Interleukin-33
keywords: Treg cells; aging; macrophages; muscle regeneration; myopathies; parabiosis