1334 Functional maturation of melanocyte stem cells requires Treg-PPARγ axis

Early life is a critical period for the development of solid organs and immune system. Regulatory T cells (Tregs) are present in skin during first week life, but their function neonatal unknown. We used Foxp3-DTR transgenic mice to assess importance Tregs. Histology, flow cytometry whole transcriptome was analyzed understand mechanisms Treg-mediated homeostasis. A peak expression Treg activation markers observed on postnatal day 9 (P9). Depletion early Tregs (eTregs) P6 P8 caused 20% reduction pigmentation P28 (p=0.0007). By contrast, developed normally after depletion late (lTregs) P10 P12. Whole RNA-seq performed 1 last identify immediate transcriptomic changes. Melanocyte marker genes, such as Dct, PPARγ target genes were downregulated only eTregs, not lTregs. An administration antagonist, T0070907, similarly leads defective (p=0.0017). Additionally, agonist, GW1929, restores homeostatic level Treg-depleted mice. Single cell analysis if PPARγpathway involved diseases human melanocytes. scRNA-seq revealed higher melanocyte comparison adult Similarly, elevated healthy melanocytes lesional vitiligo patients. report novel finding that P6-P8 represents window Treg-PPARγ axis defines melanogenic Disruption this results abrogation skin. This signaling pathway differentially regulated disrupted vitiligo. Our suggests stage disruption pathway, with implications