Predominant expression of interleukin (IL)-17 in chronic alopecia areata compared to IFN-γ in pathogenic Th17 cells, tissue-resident memory T cells and natural killer cells

Background: Alopecia areata (AA) is an organ-specific autoimmune disease resulting from the attack of hair follicle (HF) autoantigens through a T-cell-mediated mechanism. If there is a depletion of mTregs in HFs, especially around both hair bulge and hair bulb, it could be related to patchy hair loss in the scalp and may affect AA pathogenesis. Objectives: we investigated the possible contributory role of tissue-resident memory T cells (TRMs) and memory regulatory T cells (mTregs), compared to cytotoxic T lymphocytes and Th17 lymphocytes, in the immunopathogenesis of chronic AA. Methods: Three hundred and sixty-seven patients with AA who had biopsies performed in Dong-A University Hospital between January 1994 and April 2019 were retrospectively reviewed. To investigate the expression of immunoregulatory molecules, we underwent double direct immunofluorescence with paraffin sections from nine AA patients under classified according to the histopathological grading of Uno and Orecchia's classification. Results: The number of lesional Foxp3+ Tregs was significantly decreased with an increase in the severity of histopathological gradings at both the hair bulge and hair bulb, in the following order: Type 1>type 2>type 3 AA lesions. The number of CD8(+) CD69(+) TRM cells at both the HF bulge and bulb was increased with the severity of histopathological grades. CD49a was not expressed in the hair bulge and bulb in any type of AA. As for the expression profile of effector T cells, interleukin (IL)-17 was expressed in a denser pattern around the hair bulge with more severe histopathological grading, but IFN-gamma was expressed only at the hair bulge of type 1 AA. Lesional IL-17 around the hair bulb also increased with the severity of histopathological grade. In contrast, IFN-gamma was expressed in the hair bulb only in type 1 AA. Conclusions: The insidious destruction of hair bulge stem cells and hair bulb matrix stem cells, which is mediated by Th17 lymphocytes and cytotoxic T lymphocyte infiltration, results in more severe hair loss in patients with chronic AA. IL-17 may play a more important role in the pathogenesis of chronic AA than IFN-gamma.