Involvement of IL-17F via the induction of IL-6 in psoriasis

Arch Dermatol Res. 2010 Sep;302(7):499-505. doi: 10.1007/s00403-010-1033-8. Epub 2010 Feb 11.


Recently, the important role of T helper 17 (Th17) cells in psoriasis has been clarified; however, the role of IL-17F produced by Th17 cells is still not fully understood. IL-6 exhibits multiple biologic functions, such as regulation of immunological responses including those in psoriatic reactions. Therefore, we examined the production of IL-6 protein in normal human epidermal keratinocytes (NHEKs) stimulated by IL-17F, TNF-alpha, IL-17A, and IL-17A in combination with TNF-alpha, and PBS control. We then examined the expression of IL-6 mRNA in mouse skin after intradermal injection of IL-17F. Finally, IL-17F expression in skin biopsy specimens from psoriasis patients was examined by immunohistochemistry. The results showed that IL-17F induced production of IL-6 in NHEKs in a time-dependent manner. This could be attenuated by chimeric inhibitor blocking the IL-17 receptor. The amounts of IL-6 stimulated by IL-17F were much higher than those stimulated by TNF-alpha or IL-17A. IL-6 was also significantly upregulated via synergistic stimulation with IL-17A plus TNF-alpha. The expression of IL-6 mRNA 24 h after IL-17F injection in the mouse skin was 3.2-fold higher than that in the control group. Immunohistochemistry of inflammatory cells in the dermis demonstrated a large number of CD4(+) T cells showing IL-17F positivity in psoriatic skin lesions, but few or none in non-lesional psoriatic skin. Our results indicate that IL-17F produced by CD4(+) T cells causes the inflammation in psoriasis partly through induction of IL-6 in keratinocytes.

MeSH terms

  • Animals
  • Biopsy
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology
  • Cells, Cultured
  • Female
  • Humans
  • Immunohistochemistry
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Interleukin-17 / pharmacology
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / genetics
  • Keratinocytes / drug effects
  • Keratinocytes / immunology
  • Keratinocytes / metabolism*
  • Keratinocytes / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Psoriasis / immunology*
  • Psoriasis / pathology
  • Receptors, Interleukin-17 / antagonists & inhibitors
  • Recombinant Fusion Proteins / pharmacology
  • Skin / drug effects
  • Skin / pathology


  • Il17ra protein, mouse
  • Interleukin-17
  • Interleukin-6
  • Receptors, Interleukin-17
  • Recombinant Fusion Proteins