The distinct role and regulatory mechanism of IL-17 and IFN-γ in the initiation and development of plaque vs guttate psoriasis

J Dermatol Sci. 2018 Oct;92(1):106-113. doi: 10.1016/j.jdermsci.2018.07.001. Epub 2018 Jul 7.

Abstract

Background: Few studies have explored the differences of immunopathogenesis in plaque vs guttate psoriasis, especially on the inhibitory role of regulatory T cells (Tregs) on IL-17/ IFN-γ production and the impact of CD4+T cells on keratinocytes.

Objective: To investigate the percentage and inhibitory function of CD4+CD25highTreg and differential expressions of IL-17/ IFN-γ in plaque vs guttate psoriasis, and the effects of CD4+T cells on the proliferation of keratinocytes.

Methods: Peripheral blood mononuclear cells (PBMCs) were prepared from patients with the plaque and guttate psoriasis. The percentage of CD4+CD25high Tregs, IL-17/IFN-γ- producing CD4+ or CD8+T cells, and apoptosis and cell cycle of Hacat cells were determined by flow cytometry. The level of IFN-γ in supernatants was analyzed by ELISA.

Results: The percentage of CD4+CD25highTregs in plaque psoriasis was significantly increased, and they can inhibit IFN-γ production from CD4+CD25- effector T cells. The percentage of CD8+IFN-γ+cells was also significantly increased in plaque psoriasis, and these cells positively correlated with disease severity. The percentage of CD4+CD25highTregs was decreased and CD4+IFN-γ+/IFN-γ+IL-17+ cells were predominantly increased in guttate psoriasis. CD4+T cells from guttate psoriasis induce apoptosis of keratinocytes while they promote the proliferation of keratinocytes in plaque psoriasis by decreasing late apoptosis and increasing the percentage of G1 phase.

Conclusion: There was considerable discrepancy of the phenotype and function of T cells between plaque vs guttate psoriasis. IFN-γ and IL-17 from CD4+T cells play a crucial role in guttate psoriasis, however, IFN-γ and IL-17 from CD8+T cells are more important in the immunopathogenesis of plaque psoriasis.

Keywords: IFN-γ; IL-17; Plaque psoriasis; Treg; guttate psoriasis.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Apoptosis
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Case-Control Studies
  • Cell Communication
  • Cell Line
  • Cell Proliferation*
  • Female
  • G1 Phase Cell Cycle Checkpoints
  • Humans
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism*
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism*
  • Keratinocytes / immunology
  • Keratinocytes / metabolism*
  • Keratinocytes / pathology
  • Male
  • Middle Aged
  • Phenotype
  • Psoriasis / classification
  • Psoriasis / immunology
  • Psoriasis / metabolism*
  • Psoriasis / pathology
  • Signal Transduction
  • Skin / immunology
  • Skin / metabolism*
  • Skin / pathology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • Young Adult

Substances

  • IFNG protein, human
  • Interleukin-17
  • Interferon-gamma