Chronic plaque-type psoriasis is a Th17 disease driven by IL-17. In addition to IL-17, Th17 cells produce other cytokines including IL-26, a member of IL-10 cytokine family. The relation between IL-26-producing and IL-17-producing Th17 cells is unknown. By comparing the production of IL-26 and IL-17 in acute and chronic forms of psoriasis, we found a dichotomous expression of these cytokines by T cells. Immunofluorescence analysis of skin lesions showed increased numbers of IL-26-producing T cells with few IL-17-producing T cells in acute psoriasis, including erythrodermic and guttate psoriasis, whereas large numbers of IL-17-producing T cells and few IL-26-producing T cells characterized chronic plaque psoriasis. Furthermore, intracellular cytokine expression analysis revealed that circulating memory Th17 cells contained a subset of IL-26-producing T cells that was distinct from IL-17-producing T cells. Their differentiation from naïve T cells was more rapid and did not require TGFb contrary to IL-17-producing T cells, indicating that IL-26-producing T cells was a distinct early differentiating subset of Th17 cells. Interestingly, IL-26 was able to induce TGFb expression in keratinocytes, suggesting that IL-26-producing T cells drive the subsequent generation of IL-17-producing T cells via TGFb induction in the skin. Together, our findings indicate that IL-26 producing T cells are an early differentiating subset of Th17 cells that promote induction of IL-17 producing T cells in the skin through TGFb induction, providing new insights and potential therapeutic targets to block the pathogenic IL-17 pathway in psoriasis.

A distinct Th17 cell subset producing IL-26 promotes expression of IL-17 in the skin through induction of TGFb