Immune Regulation in Hair Follicle Protection and Hair Regeneration: Insights from the Collapse of Immune Privilege in Alopecia Areata and Targeted Immunotherapy

Under physiological conditions, hair follicle immune privilege protects hair follicles through spatial isolation, immune regulators (e.g., transforming growth factor beta, programmed death-ligand 1), and regulatory T cells. In addition, immune cells actively facilitate hair follicle regeneration by regulating the hair cycle via pathways such as Jag1-Notch, Janus Kinase–Signal Transducer and Activator of Transcription, and Wnt pathways. They also promote wound-induced hair neogenesis through macrophage- and regulatory T cell-mediated mechanisms. In alopecia areata, stress-induced collapse of hair follicle immune privilege initiates autoantigen presentation, thereby triggering an autoreactive inflammatory loop. This review, based on literature retrieved from PubMed, Web of Science, and Embase databases (January 2018–June 2025; approximately 120 studies included), summarizes recent advances in understanding immune regulation of hair follicle immune privilege maintenance, its breakdown in alopecia areata, and its implications for immune-guided hair follicle regeneration. Current therapies, including corticosteroids and Janus Kinase inhibitors, provide symptomatic relief but fail to prevent relapse. Emerging targeted immunotherapies, such as inhibitors of inflammatory pathways and modulation of regulatory T cells, offer promising prospects for the treatment of alopecia areata.