IL-17A-producing gamma delta T cells promote muscle regeneration in a microbiota-dependent manner

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 gamma delta T cells in promoting healthy tissue recovery after injection of cardiotoxin into murine hindlimb muscle. Within a few days of injury, IL-17A-producing gamma delta T cells displaying primarily V gamma 6(+) 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(+) gamma delta T cells with recombinant IL-17A largely reversed their inflammatory and reparative defects. Unexpectedly, the accumulation and influences of gamma delta T 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. Mann et al. report the accrual of a population of IL-17-producing gamma delta T cells shortly after acute injury of murine skeletal muscle. This microbiota-dependent population promotes muscle repair in an IL-17A- and neutrophil-dependent manner.