Interleukin-17 is produced by both Th1 and Th2 lymphocytes, and modulates interferon-gamma- and interleukin-4-induced activation of human keratinocytes

J Invest Dermatol. 2000 Jul;115(1):81-7. doi: 10.1046/j.1523-1747.2000.00041.x.


Interleukin-17 is a T-cell-derived cytokine, detected in skin affected by allergic contact dermatitis and psoriasis, which regulates keratinocyte expression of adhesion molecules and chemokines. In this study, we have analyzed whether interleukin-17 production segregates with a particular T helper (Th) cell subset, and have examined the capacity of interleukin-17 to modulate the activation of keratinocytes induced by Th1 and Th2 cytokines. A panel of 80 nickel-specific CD4+ T cell clones (36 Th0, 30 Th1, and 14 Th2) was isolated from peripheral blood or lesional skin of allergic contact dermatitis patients. Significant amounts (> 50 pg per ml) of interleukin-17 were released by about 50% of activated Th0, Th1, and Th2 cells. Interleukin-17 alone and in cooperation with interleukin-4, or to a lesser extent with interferon-gamma, decreased the interleukin-1 receptor antagonist to interleukin-1alpha ratio in the supernatants as well as in cell lysates from keratinocytes. In addition, interleukin-17 stimulated the release of growth-regulated oncogene-alpha, granulocyte-macrophage colony stimulating factor, and interleukin-6, with synergistic or additive effects when used together with interferon-gamma or interleukin-4. Interleukin-17 and interleukin-4 also increased stem cell factor release, a function that was inhibited by interferon-gamma. Moreover, interleukin-17 and interleukin-4 enhanced interferon-gamma-induced expression of intercellular adhesion molecule 1, but not CD40, on keratinocytes. The constitutive expression of interleukin-17 and interferon-gamma receptors on keratinocytes was not modulated by interleukin-17, interferon-gamma, or interleukin-4, whereas the interleukin-4 receptor was significantly downregulated by interferon-gamma. As a whole, the results indicate that interleukin-17 can participate relevantly in T-cell-mediated skin immune responses by amplifying both interferon-gamma- and interleukin-4-induced activation of keratinocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemokine CXCL1
  • Chemokines, CXC*
  • Chemotactic Factors / metabolism
  • Clone Cells
  • Dermatitis, Allergic Contact / immunology
  • Epitopes
  • Growth Substances / metabolism
  • Humans
  • Immunity, Cellular
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Intercellular Signaling Peptides and Proteins*
  • Interferon-gamma / pharmacology*
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / pharmacology*
  • Interleukin-4 / pharmacology*
  • Keratinocytes / drug effects
  • Keratinocytes / immunology*
  • Keratinocytes / physiology*
  • Nickel / immunology
  • Psoriasis / immunology
  • Stem Cell Factor / metabolism
  • T-Lymphocytes, Helper-Inducer / cytology
  • Th1 Cells / cytology
  • Th1 Cells / metabolism*
  • Th2 Cells / cytology
  • Th2 Cells / metabolism*


  • CXCL1 protein, human
  • Chemokine CXCL1
  • Chemokines, CXC
  • Chemotactic Factors
  • Epitopes
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-17
  • Stem Cell Factor
  • Intercellular Adhesion Molecule-1
  • Interleukin-4
  • Nickel
  • Interferon-gamma