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

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

Author information

1
Department of Dermatology, University of Maryland, Baltimore, Maryland, USA.
2
Department of Dermatology, University of Maryland, Baltimore, Maryland, USA; Department of Microbiology/Immunology, University of Maryland, Baltimore, Maryland, USA.
3
Department of Dermatology, University of Maryland, Baltimore, Maryland, USA; Department of Dermatology, La Sapienza University, Rome, Italy.
4
Drexel University, Philadelphia, Pennsylvania, USA.
5
Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, USA.
6
Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.
7
Department of Dermatology, University of Maryland, Baltimore, Maryland, USA; Department of Microbiology/Immunology, University of Maryland, Baltimore, Maryland, USA. Electronic address: agasp001@umaryland.edu.

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.

PMID:
24487305
PMCID:
PMC4303591
DOI:
10.1038/jid.2014.61
[Indexed for MEDLINE]
Free PMC Article

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