Potential role of IL-17-producing CD4/CD8 double negative αβ T cells in psoriatic skin inflammation in a TPA-induced STAT3C transgenic mouse model.

Background: Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders and is accompanied by erythematous scaly plaques. There is growing evidence that the IL-23/Th17 axis plays a critical role in development of the disease. It was recently shown that in addition to CD4 Th17 cells, various IL-17-producing cell subsets such as CD8 Tc17 cells, dermal γδ T cells, and innate lymphoid cells are also involved in the development of psoriatic inflammation in humans.

Objective: To investigate which subsets of IL-17-producing cells are involved in psoriasis-like skin inflammation in a TPA (tumor promoter 12-O-tetradecanoylphorbol-13-acetate)-induced K14.Stat3C mouse model.

Method: Skin-infiltrating cells were isolated from inflamed lesions of TPA-treated K14.Stat3C transgenic mice, and analyzed for IL-17 producing cell subsets by flow cytometry.

Results: We observed significantly increased numbers of IL-17-producing CD4 T cells, CD8 T cells and dermal γδ T cells in TPA-induced skin lesions of K14.Stat3C mice. Additionally, we found that another IL-17-producing T cell subset, αβ-TCR CD4CD8 double negative T cells (DN αβ T cells), was also increased in lesional skin. These IL-17-producing DN αβ T cells are NK1.1 negative, suggesting they are not natural killer T cells or mucosal associated invariant T cells. As well as other IL-17-producing cells, DN αβ T cells in the inflamed skin can also respond to IL-23 stimulation to produce IL-17. It is also suggested that DN αβ T cells may express retinoic acid-related orphan receptor gamma t and CC chemokine receptor 6.

Conclusion: In TPA-induced lesional skin of K14.Stat3C mice, IL-17-producing CD4 Th17 cells, CD8 Tc17 cells, dermal γδ T cells and TCR cells probably containing ILCs all participated in skin inflammation, which is similar to human clinical psoriatic features. Furthermore, we showed for the first time the possibility that an IL-17-producing DN αβ T cell subset is also involved in psoriatic inflammation.