Vδ1+ T-Cells Are Stress-Sentinels in Human Skin and Are Implicated in Alopecia Areata Pathogenesis

The study investigated the role of Vδ1+ T-cells in human skin, particularly their impact on hair follicles (HFs) and their involvement in alopecia areata (AA) pathogenesis. Vδ1+ T-cells were found to be stress-sentinels that, when activated, caused HF cytotoxicity, dystrophy, premature catagen, and immune privilege collapse in stressed HFs, similar to CD8+ T-cells. These effects were linked to the overexpression of the stress-induced NKG2D ligand, MICA, and were inhibited by blocking antibodies against INFγ, CD1d, or MICA. The study also found dense infiltrates of NKG2D- and INFγ-overexpressing Vδ1+ T-cells in AA patients' lesional HFs and in experimentally induced AA lesions in human scalp xenotransplanted onto SCID mice. These findings suggested that targeting the excessive activities of NKG2D+Vδ1+ T-cells could be a promising therapy for AA and related autoimmune diseases.