title: Poor Repair of Skeletal Muscle in Aging Mice Reflects a Defect in Local, Interleukin-33-Dependent Accumulation of Regulatory T Cells.
abstract: Normal repair of skeletal muscle requires local expansion of a special population of Foxp3(+)CD4(+) regulatory T (Treg) cells. Such cells failed to accumulate in acutely injured muscle of old mice, known to undergo ineffectual repair. This defect reflected reduced recruitment of Treg cells to injured muscle, as well as less proliferation and retention therein. Interleukin-33 (IL-33) regulated muscle Treg cell homeostasis in young mice, and its administration to old mice ameliorated their deficits in Treg cell accumulation and muscle regeneration. The major IL-33-expressing cells in skeletal muscle displayed a constellation of markers diagnostic of fibro/adipogenic progenitor cells and were often associated with neural structures, including nerve fibers, nerve bundles, and muscle spindles, which are stretch-sensitive mechanoreceptors important for proprioception. IL-33(+) cells were more frequent after muscle injury and were reduced in old mice. IL-33 is well situated to relay signals between the nervous and immune systems within the muscle context.
authors.affiliation: Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Wilson
authors.initials: W
authors.lastname: Kuswanto
authors.affiliation: Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Dalia
authors.initials: D
authors.lastname: Burzyn
authors.affiliation: Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Marisella
authors.initials: M
authors.lastname: Panduro
authors.affiliation: Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Kathy K
authors.initials: KK
authors.lastname: Wang
authors.affiliation: Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors.forename: Young Charles
authors.initials: YC
authors.lastname: Jang
authors.affiliation: Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Joslin Diabetes Center, Boston, MA 02215, USA; Paul F Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Wagers
authors.affiliation: Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Benoist
authors.affiliation: Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: cbdm@hms.harvard.edu.
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
mesh_terms: D050156:Adipogenesis / Q000276:immunology; D000375:Aging / Q000276:immunology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D006706:Homeostasis; D006801:Humans; D000067596:Interleukin-33 / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology*; D009412:Nerve Fibers / Q000502:physiology; D015213:Neuroimmunomodulation; D012038:Regeneration / Q000276:immunology; D013234:Stem Cells / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014945:Wound Healing
chemical_list: D015415:Biomarkers; D000067596:Interleukin-33