A developmentally restricted γδ T cell-IL-17A axis supports mouse heart regeneration
Abstract
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.
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BibTeX
@article{aguilar2026developmentally,
title = {{A developmentally restricted γδ T cell-IL-17A axis supports mouse heart regeneration}},
author = {Stephanie Vargas Aguilar and Matthieu Dos Santos and Wei Tan and Efrain Sanchez-Ortiz and Kenian Chen and Hui Li and Lin Xu and Ning Liu and Eric N. Olson},
journal = {Cell Reports},
year = {2026},
month = oct,
doi = {10.1016/j.celrep.2026.118100},
url = {https://linkinghub.elsevier.com/retrieve/pii/S2211124726011794},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - A developmentally restricted γδ T cell-IL-17A axis supports mouse heart regeneration
AU - Stephanie Vargas Aguilar
AU - Matthieu Dos Santos
AU - Wei Tan
AU - Efrain Sanchez-Ortiz
AU - Kenian Chen
AU - Hui Li
AU - Lin Xu
AU - Ning Liu
AU - Eric N. Olson
PY - 2026
DA - 2026/10/01
JO - Cell Reports
DO - 10.1016/j.celrep.2026.118100
UR - https://linkinghub.elsevier.com/retrieve/pii/S2211124726011794
AB - 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.
SN - 2211-1247
ER -