Neonatal regulatory T cells persist into adulthood across multiple tissues with high enrichment in the skin
- Morgane Hilaire
- Angélina Mimoun
- Léonie Cagnet
- Rémy Villette
- Aristeidis Roubanis
- Hugo Sentenac
- Benoît L. Salomon
2025-10-03
Foxp3 + regulatory T cells (T regs ) reside in both lymphoid and nonlymphoid organs, where they play a crucial role in immune tolerance and tissue homeostasis. In mice, T regs begin colonizing these tissues shortly after birth, contributing to long-term immune response regulation therein. However, the kinetics of T reg generation across different tissues remains unclear. Here, we investigate T reg ontogeny from birth to adulthood in various tissues. In lymphoid organs, the adult T reg pool is continuously replenished with cells generated at different ages. In contrast, the skin retains a large fraction of T regs that colonize the tissue during the neonatal period, with minimal turnover in adulthood. The liver, lungs, and colon exhibit intermediate T reg renewal dynamics. Notably, neonatal T regs that persist into adulthood display a more activated phenotype and express markers associated with tissue-resident T regs and type 2 immunity. Our findings reveal tissue-specific differences in T reg generation kinetics and highlight a major phenotypic shift between neonatal and adult-derived T regs .