IL-22-producing "T22" T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing T_H17 T cells

Background: Psoriasis and atopic dermatitis (AD) are common inflammatory skin diseases. An upregulated T_H17/IL-23 pathway was demonstrated in psoriasis. Although potential involvement of T_H17 T cells in AD was suggested during acute disease, the role of these cells in chronic AD remains unclear. Objective: To examine differences in IL-23/T_H17 signal between these diseases and establish relative frequencies of T-cell subsets in AD. Methods: Skin biopsies and peripheral blood were collected from patients with chronic AD (n = 12) and psoriasis (n = 13). Relative frequencies of CD4⁺ and CD8⁺ T-cell subsets within these 2 compartments were examined by intracellular cytokine staining and flow cytometry. Results: In peripheral blood, no significant difference was found in percentages of different T-cell subsets between these diseases. In contrast, psoriatic skin had significantly increased frequencies of T_H1 and T_H17 T cells compared with AD, whereas T_H2 T cells were significantly elevated in AD. Distinct IL-22-producing CD4⁺ and CD8⁺ T-cell populations were significantly increased in AD skin compared with psoriasis. IL-22⁺CD8⁺ T-cell frequency correlated with AD disease severity. Conclusion: Our data established that T cells could independently express IL-22 even with low expression levels of IL-17. This argues for a functional specialization of T cells such that "T17" and "T22" T-cells may drive different features of epidermal pathology in inflammatory skin diseases, including induction of antimicrobial peptides for "T17" T cells and epidermal hyperplasia for "T22" T-cells. Given the clinical correlation with disease severity, further characterization of "T22" T cells is warranted, and may have future therapeutic implications.