IL-17 amplifies human contact hypersensitivity by licensing hapten nonspecific Th1 cells to kill autologous keratinocytes

J Immunol. 2010 May 1;184(9):4880-8. doi: 10.4049/jimmunol.0901767. Epub 2010 Mar 31.

Abstract

Th17 is a newly identified lineage of effector T cells involved in autoimmunity and immune responses to pathogens. We demonstrate in this study the pathogenic role of IL-17-producing CD4(+) T lymphocytes in allergic contact dermatitis (ACD) to skin-applied chemicals. IL-17(+) T cells infiltrate ACD reactions and predominantly distribute at the site of heavy spongiosis. Skin IL-17(+) T cells were functionally and phenotypically heterogeneous: although pure Th17 prevailed in ACD skin, hapten responsiveness was restricted to Th1/IL-17 (IFN-gamma(+)IL-17(+)) and Th0/IL-17 (IFN-gamma(+)IL-17(+)IL-4(+)) fractions, and to lesser extent Th2/IL-17 cells. In the IFN-gamma-dominated ACD environment, IL-17-releasing T cells affect immune function of keratinocytes by promoting CXCL8, IL-6, and HBD-2 production. In addition, compared with Th1, supernatants from Th1/IL-17 T cells were much more efficient in inducing ICAM-1 expression on keratinocytes and keratinocyte-T cell adhesiveness in vitro. As a consequence, exposure to combined IFN-gamma and IL-17 rendered keratinocytes susceptible to ICAM-1-dependent Ag nonspecific T cell killing. Thus, IL-17 efficiently amplifies the allergic reaction by rendering virtually all of the T lymphocytes recruited at the site of skin inflammation capable to directly contribute to tissue damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Apoptosis / immunology
  • Cell Communication / immunology
  • Cell Death / immunology
  • Cell Movement / immunology
  • Cells, Cultured
  • Chemokines / metabolism
  • Clone Cells
  • Coculture Techniques
  • Cytokines / metabolism
  • Dermatitis, Allergic Contact / immunology*
  • Dermatitis, Allergic Contact / metabolism
  • Dermatitis, Allergic Contact / pathology*
  • Epitopes, T-Lymphocyte / immunology*
  • Haptens / immunology*
  • Humans
  • Inflammation Mediators / physiology
  • Intercellular Adhesion Molecule-1 / physiology
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / metabolism
  • Interleukin-17 / physiology*
  • Keratinocytes / immunology*
  • Keratinocytes / metabolism
  • Keratinocytes / pathology*
  • Mice
  • Nickel / immunology*
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th1 Cells / pathology

Substances

  • Chemokines
  • Cytokines
  • Epitopes, T-Lymphocyte
  • Haptens
  • Inflammation Mediators
  • Interleukin-17
  • Intercellular Adhesion Molecule-1
  • Nickel