Background: Alopecia areata (AA) is an organ-specific autoimmune disease resulting from the attack of hair follicle (HF) autoantigens through T-cell-mediated mechanism. Beyond the hypothesis of immune privilege collapse, we suppose any change of memory regulatory T cells (mTregs) affect the balance between effector T cell subsets in AA pathogenesis. CD49a expression defines different functional subsets in Trm cells, for examples, CD8+ CD49a+ Trm cells produce IFN-γ in vitiligo lesions, whereas CD8+CD49a- Trm cells produce IL-17 in psoriatic lesions. The role of mTregs and Trm cells has not been studied yet in AA lesions.
Objectives: To determine whether effector T cells including Th17 cells and cytotoxic T cells are associated with intralesional localizations of Trm cells and mTregs, which could be expected to reflect the clinicohistopathological severity and immunopathogenesis.
Methods: We investigated the correlation between the effector T cells-related cytokines (IL-17 and IFN-γ) and the infiltrations of Trm cells and mTregs around the hair bulb/bulge in 9 chronic AA patients according to histopathological grades through double immunofluorescence.
Results: Lesional IL-17 in both HF bulge and bulb was significantly increased in parallel with the severer histopathologic gradings. In contrast, IFN-γ was expressed in a lesser degree. CD8+CD49a-Trm cells in both HF bulge and bulb were increased in parallel with the severer histopathologic gradings. Importantly, infiltrated Foxp3+mTregs were decreased in an inverse manner to the severer clinicohistopathologic gradings of AA.
Conclusions: These results showed significantly higher IL-17 expression and denser infiltrations of CD8+CD49a-Trm cells in lesion in AA patients, which may highlight another functional role of these cytokines in the pathogenesis of AA.

More Expression of IL-17 than IFN-γ from CD49a-negative Tissue-Resident Memory T (Trm) cells at the Hair Bulge and Hair Bulb Region in the Scalp of Chronic Alopecia Areata Patients according to the Foxp3+mTregs depletion.