The Role of Hair Follicle Immune Privilege Collapse in Alopecia Areata: Status and Perspectives

Alopecia areata (AA) may represent a CD8+T cell–mediated, organ-specific autoimmune disease in which as yet elusive autoantigens are recognized, once they become exposed by ectopic major histocompatibility complex class I expression by anagen hair follicles (HFs) that have lost their relative immune privilege (IP). On this basis, AA research is chiefly challenged with identifying the autoreactive CD8+T cells and their cognate autoantigens as well as key inducers of HF-IP collapse and “HF-IP guardians” that prevent and/or can restore IP collapse. However, natural killer group 2D–positive (NKG2D+) cells (incl. NK, NKT, and CD8+T cells) and NKG2D–activating ligands from the MICA (MHC I–related chain A) family may also have a key role in AA pathogenesis, as a massive infiltrate of IFN-γ-secreting NKG2D+ cells alone suffices to induce the AA phenotype. Therefore, we speculate that AA may represent a stereotypic, but distinct HF response pattern to inflammatory insults associated with HF-IP collapse.