IL-17A-producing γδT cells promote muscle regeneration in a microbiota-dependent manner.

Autor:	Mann AO; Department of Immunology, Harvard Medical School, Boston, MA.; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA., Hanna BS; Department of Immunology, Harvard Medical School, Boston, MA.; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA., Muñoz-Rojas AR; Department of Immunology, Harvard Medical School, Boston, MA.; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA., Sandrock I; Institute of Immunology, Hannover Medical School, Hannover, Germany., Prinz I; Institute of Immunology, Hannover Medical School, Hannover, Germany.; Institute of Systems Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Benoist C; Department of Immunology, Harvard Medical School, Boston, MA.; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA., Mathis D; Department of Immunology, Harvard Medical School, Boston, MA.; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2022 May 02; Vol. 219 (5). Date of Electronic Publication: 2022 Apr 05.
DOI:	10.1084/jem.20211504
Abstrakt:	Subsequent to acute injury, skeletal muscle undergoes a stereotypic regenerative process that reestablishes homeostasis. Various types of innate and adaptive immunocytes exert positive or negative influences at specific stages along the course of muscle regeneration. We describe an unanticipated role for γδT cells in promoting healthy tissue recovery after injection of cardiotoxin into murine hindlimb muscle. Within a few days of injury, IL-17A-producing γδT cells displaying primarily Vγ6+ antigen receptors accumulated at the wound site. Punctual ablation experiments showed that these cells boosted early inflammatory events, notably recruitment of neutrophils; fostered the proliferation of muscle stem and progenitor cells; and thereby promoted tissue regeneration. Supplementation of mice harboring low numbers of IL-17A+ γδT cells with recombinant IL-17A largely reversed their inflammatory and reparative defects. Unexpectedly, the accumulation and influences of γδT cells in this experimental context were microbiota dependent, unveiling an orthogonal perspective on the treatment of skeletal muscle pathologies such as catastrophic wounds, wasting, muscular dystrophies, and myositides. (© 2022 Mann et al.)
Databáze:	MEDLINE
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