Human Regulatory Gamma Delta T Lymphocytes as Novel Autoimmunity-Protective Cells: Lessons from Alopecia Areata

This study investigates the role of human regulatory γδT cells (γδTregs) in alopecia areata (AA), a common autoimmune hair loss disorder. The research found that γδTregs are more prevalent in lesional AA skin compared to non-lesional or healthy skin. In experiments using human scalp skin xenotransplants on mice, γδTregs, pre-activated with IL-2, IL-15, and zoledronate, were able to prevent AA lesion development and promote hair regrowth by reducing lymphocytic infiltration and restoring hair follicle immune privilege. Additionally, γδTregs co-cultured with stressed human scalp hair follicles mitigated immune privilege collapse and enhanced keratinocyte proliferation, primarily through IL-10 and TGF-β1 secretion. These findings suggest that γδTregs could be a novel therapeutic target for CD8+ T cell-dependent autoimmune diseases like AA.