Early skin seeding regulatory T cells modulate PPARγ-dependent skin pigmentation

Area of Science:

• Immunology
• Developmental Biology
• Dermatology

Background:

• Tissue homeostasis relies on immune cell and stem cell interactions.
• Neonatal skin harbors regulatory T cells (Tregs) with an unexplored role.
• Early skin Tregs (ETregs) are present from postnatal day 3.

Purpose of the Study:

• Investigate the function of ETregs in neonatal skin pigmentation.
• Determine the molecular mechanisms linking ETregs to skin development.
• Explore the role of PPARγ signaling in this process.

Main Methods:

• Experimental depletion of ETregs in neonatal mice.
• Transcriptomic and single-cell RNA sequencing of skin.
• Analysis of melanocyte stem cells (MeSCs) and pigmentation.
• Investigation of PPARγ pathway activity.

Main Results:

• Punctual ETreg depletion impaired skin pigmentation mediated by hair follicle (HF) MeSCs.
• Loss of ETregs altered MeSC markers and perturbed PPARγ target genes in HF.
• PPARγ signaling was diminished in HF epithelium upon ETreg loss.
• Vitiligo skin showed reduced PPARγ pathway activation in HF cells.

Conclusions:

• ETregs are critical for maintaining HF PPARγ signaling in neonatal skin.
• This signaling is vital for MeSC-mediated skin pigmentation during postnatal development.
• Dysregulation of this pathway may contribute to skin depigmentation disorders like vitiligo.