The IL-17A-producing CD8 + T-cell population in psoriatic lesional skin comprises mucosa-associated invariant t cells and conventional t cells

摘要

IL-17A is pivotal in the etiology of psoriasis, and CD8 + T cells with the ability to produce this cytokine (Tc17 cells) are over-represented in psoriatic lesions. Here we demonstrate that the frequency of Tc17 cells in peripheral blood of psoriasis patients correlated with the clinical severity of the disease. Analysis of cutaneous-associated lymphocyte antigen expression showed that the blood Tc17 population contains a significantly higher proportion of cells with skin-homing potential compared with the CD8 + T-cell population lacking IL-17A/IL-22 expression. IL-17A-producing CD8 + T cells in blood have previously been reported to belong mainly to the mucosa-associated invariant T-cell (MAIT cell) lineage characterized by TCR V7.2 chain, CD161, IL-18R, and multidrug transporter ABCB1 expression. We demonstrate the presence of CD8 + MAIT cells in the dermis and epidermis of psoriatic plaques, as well as healthy skin; however, IL-17A-producing CD8 + MAIT cells were predominantly found in psoriatic skin. Notably, we observed IL-17A production in a large proportion of psoriatic plaque-derived CD8 + T cells devoid of MAIT cell characteristics, likely representing conventional CD8 + T cells. In conclusion, we provide supporting evidence that implicates Tc17 cells in the pathogenesis of psoriasis and describe the presence of innate CD8 + MAIT cells in psoriatic lesions as an alternative source of IL-17A.