Memory regulatory T cells reside in human skin

Area of Science:

• Immunology
• Dermatology
• Cell Biology

Background:

• Regulatory T cells (Tregs) expressing Foxp3 are crucial for immune homeostasis and preventing autoimmunity.
• A subset of Tregs with memory properties (mTregs) was previously identified in murine skin.
• Understanding human skin-resident Tregs is vital for tissue inflammation research.

Purpose of the Study:

• To investigate the presence and characteristics of memory Tregs (mTregs) in normal and inflamed human skin.
• To compare human cutaneous mTregs with those in peripheral blood.
• To explore the role of mTregs in inflammatory skin conditions like psoriasis.

Main Methods:

• Analysis of Treg populations in human skin biopsies and peripheral blood.
• Characterization of cell surface markers and cytokine production.
• T-cell receptor (TCR) sequencing to assess antigen recognition.
• Comparison of mTreg behavior in steady-state versus inflamed skin (psoriasis).

Main Results:

• Nearly all Tregs in normal human skin exhibit an activated memory phenotype (cutaneous mTregs).
• Cutaneous mTregs display distinct surface markers and cytokine profiles compared to blood mTregs.
• mTregs are enriched in hair follicles and areas of high hair density.
• TCR analysis suggests mTregs recognize different antigens than conventional memory T helper cells.
• In psoriasis, mTregs expand, proliferate, and exhibit reduced IL-17 production.

Conclusions:

• A distinct subset of Tregs, identified as mTregs, stably resides in human skin, primarily associated with hair follicles.
• These skin-resident mTregs possess unique characteristics compared to their counterparts in circulation.
• Dysfunctional mTregs, characterized by altered proliferation and cytokine profiles, may contribute to the pathogenesis of inflammatory skin diseases like psoriasis.