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

J Dermatol Sci. 2017 Jan;85(1):27-35. doi: 10.1016/j.jdermsci.2016.10.007. Epub 2016 Oct 19.


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.

Keywords: Double negative αβ T cell; IL-17; IL-23; Psoriasis model; Stat3 transgenic mouse; Th17.

MeSH terms

  • Animals
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Disease Models, Animal
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Inflammation / immunology*
  • Interleukin-17 / metabolism*
  • Interleukin-23 Subunit p19 / metabolism*
  • Mice
  • Mice, Transgenic
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Psoriasis / chemically induced
  • Psoriasis / immunology*
  • Receptors, CCR6 / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Skin / cytology
  • Skin / immunology
  • Skin / metabolism
  • T-Lymphocyte Subsets / metabolism*
  • Tetradecanoylphorbol Acetate / analogs & derivatives
  • Tetradecanoylphorbol Acetate / toxicity


  • CCR6 protein, mouse
  • CD4 Antigens
  • CD8 Antigens
  • Il17a protein, mouse
  • Il23a protein, mouse
  • Interleukin-17
  • Interleukin-23 Subunit p19
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, CCR6
  • Rorc protein, mouse
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • 4-O-methyl-12-O-tetradecanoylphorbol 13-acetate
  • Tetradecanoylphorbol Acetate