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

ABSTRACT: Subsequent to acute injury, skeletal muscle undergoes a stereotypic regenerative process that re-establishes 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 gdT cells in promoting healthy tissue recovery after injection of cardiotoxin into murine hindlimb muscle. Within a few days of injury, IL-17A-producing gdT cells displaying primarily Vg6+ 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+ gdT cells with recombinant IL-17A largely reversed their inflammatory and reparative defects. Unexpectedly, the accumulation and influences of gdT 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE190588 | GEO | 2022/04/01

REPOSITORIES: GEO

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