A developmentally restricted γδ T cell-IL-17A axis supports mouse heart regeneration.

Mammalian heart regeneration is restricted to a brief postnatal period during which neonatal-specific mechanisms, including a tightly regulated immune response, enable tissue repair. Here, we show that cardiac injury during the regenerative window induces the accumulation of a distinct γδ T cell population that is absent from older, non-regenerative hearts. Following injury, these cells serve as a rapid source of IL-17A, which shapes the timing and composition of the neonatal immune response. Genetic ablation of γδ T cells or disruption of IL-17 signaling limits heart regeneration and results in dysregulated immune cell infiltration and impaired cardiac function. Mechanistically, our data suggest that γδ T cell-derived IL-17A acts on myeloid cells to initiate a rapid, self-limited inflammatory response that facilitates apoptotic cell clearance and limits sustained inflammation. Our study identifies a developmentally restricted immune axis that supports heart regeneration and advances our understanding of how neonatal-specific immune circuits shape tissue repair.