Regulatory T cells in the skin: Origin, function, and plasticity

Skin is continually exposed to external stimuli, making this frontline barrier highly susceptible to inflammatory disorders. Foxp3⁺ regulatory T cells (Tregs) are considered guardians of skin homeostasis, with functions that extend beyond immune regulation to include neuroimmunological modulation, hair cycling, and wound healing. In the resting state, skin Tregs originate from the thymus; however, the composition of the Treg population under pathological conditions remains elusive. Notably, emerging studies show that Tregs can acquire proinflammatory characteristics during the development of allergic and autoimmune diseases, raising questions about their fate and function during disease progression. This review discusses the trafficking of Tregs into the skin, their plasticity driven by proinflammatory cytokines and T helper cell lineage-defining transcription factors, and their multifaceted roles in cutaneous immunity. Together, these insights offer a perspective on Treg dynamics in skin health and disease.