Laser Capture Microdissection Reveals Transcriptional Abnormalities In Alopecia Areata Before, During, And After Active Hair Loss

The document explored the pathogenesis of alopecia areata (AA) as an autoimmune disease mediated by CD8+T cells, emphasizing the collapse of hair follicle immune privilege (HF-IP) as a crucial factor. It identified natural killer group 2D-positive (NKG2D+) cells and their ligands as significant contributors to HF-IP collapse and AA phenotype induction. The study suggested that therapeutic strategies should focus on restoring HF-IP and modulating immune responses, potentially involving nonspecific suppression of the HF response to inflammatory stimuli. It also noted the potential roles of IFN-γ, substance P, and mast cells in AA development, proposing that effective management might require a broader approach beyond targeting specific autoantigens and T cells.

A genome-wide association study conducted on 1,054 cases and 3,278 controls identified several susceptibility loci for alopecia areata, suggesting the involvement of both innate and adaptive immunity in the disease. The study highlighted significant associations with genes related to regulatory T cells, CTLA4, IL-2/IL-21, IL-2RA, and the HLA region, as well as genes expressed in the hair follicle like PRDX5 and STX17. Notably, the ULBP gene cluster on chromosome 6q25.1, encoding ligands for the natural killer cell receptor NKG2D, was implicated for the first time in autoimmune disease, with ULBP3 expression upregulated in the hair follicle during active disease. This research provided insights into the genetic basis of alopecia areata and suggested a novel mechanism involving ULBP ligand upregulation in autoimmunity.