Alopecia Areata: Animal Models Illuminate Autoimmune Pathogenesis and Novel Immunotherapeutic Strategies

Animal models have significantly advanced the understanding of alopecia areata (AA), an autoimmune disease causing hair loss. The review from 2016 discussed two key models: C3H/HeJ mice, which either naturally develop AA or do so after induction, and human scalp skin grafted onto SCID mice, which develop AA following injection of certain immune cells. These models have clarified that AA may result from the collapse of the hair follicle's immune privilege, leading to an autoimmune attack by CD8+ T cells. They have also highlighted the role of IFN-γ, IL-15, NKG2D, MICA, and ULBP3 in the disease. The C3H/HeJ mouse model has been instrumental in identifying the potential of Janus kinase (JAK) inhibitors for AA treatment, as JAK is a pathway used by both IFN-γ and IL-15. The humanized mouse model has confirmed the involvement of CD8+ T cells and NKG2D+ cells in AA and has helped identify human-specific targets for treatment, such as the potassium channel Kv1.3 and the PDE4 inhibitor apremilast, which has been shown to inhibit AA in human skin. This research underscores the importance of selecting appropriate animal models for preclinical research in human autoimmune diseases.