IL-9 regulates allergen-specific Th1 responses in allergic contact dermatitis

J Invest Dermatol. 2014 Jul;134(7):1903-1911. doi: 10.1038/jid.2014.61. Epub 2014 Jan 31.

Abstract

The cytokine IL-9, derived primarily from T-helper 9 (Th9) lymphocytes, promotes expansion of the Th2 subset and is implicated in the mechanisms of allergic asthma. We hypothesize that IL-9 also has a role in human allergic contact dermatitis (ACD). To investigate this hypothesis, skin biopsy specimens of positive patch-test sites from non-atopic patients were assayed using quantitative PCR and immunohistochemistry. The cytokines IFN-γ, IL-4, IL-17A, IL-9, and PU.1, a Th9 associated transcription factor, were elevated when compared with paired normal skin. Immunohistochemistry on ACD skin biopsies identified PU.1+ CD3+ and PU.1+ CD4+ cells, consistent with Th9 lymphocytes, in the inflammatory infiltrate. Peripheral blood mononuclear cells from nickel-allergic patients, but not nonallergic controls, show significant IL-9 production in response to nickel. Blocking studies with mAbs to HLA-DR (but not HLA-A, -B, -C) or chloroquine significantly reduced this nickel-specific IL-9 production. In addition, blockade of IL-9 or IL-4 enhanced allergen-specific IFN-γ production. A contact hypersensitivity model using IL-9(-/-) mice shows enhanced Th1 lymphocyte immune responses, when compared with wild-type mice, consistent with our human in vitro data. This study demonstrates that IL-9, through its direct effects on Th1 and ability to promote IL-4 secretion, has a regulatory role for Th1 lymphocytes in ACD.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Dermatitis, Allergic Contact / genetics
  • Dermatitis, Allergic Contact / immunology*
  • Dermatitis, Allergic Contact / metabolism
  • Female
  • Humans
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism
  • Interleukin-9 / genetics
  • Interleukin-9 / immunology*
  • Interleukin-9 / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Nickel / immunology*
  • Proto-Oncogene Proteins / metabolism
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Trans-Activators / metabolism

Substances

  • IL4 protein, human
  • IL9 protein, human
  • Interleukin-9
  • Proto-Oncogene Proteins
  • Trans-Activators
  • proto-oncogene protein Spi-1
  • Interleukin-4
  • Nickel