| Author |
Liu, Juan Harberts, Erin Tammaro, Antonella Girardi, Nicholas Filler, Renata B. Fishelevich, Rita Temann, Angela Licona-Limón, Paula Girardi, Michael Flavell, Richard A. Gaspari, Anthony A. |
| Description |
Country affiliation: United States Author Affiliation: Liu J ( Department of Dermatology, University of Maryland, Baltimore, Maryland, USA.); Harberts E ( 1] Department of Dermatology, University of Maryland, Baltimore, Maryland, USA [2] Department of Microbiology/Immunology, University of Maryland, Baltimore, Maryland, USA.); Tammaro A ( 1] Department of Dermatology, University of Maryland, Baltimore, Maryland, USA [2] Department of Dermatology, La Sapienza University, Rome, Italy.); Girardi N ( Drexel University, Philadelphia, Pennsylvania, USA.); Filler RB ( Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, USA.); Fishelevich R ( Department of Dermatology, University of Maryland, Baltimore, Maryland, USA.); Temann A ( Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.); Licona-Limón P ( Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.); Girardi M ( Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, USA.); Flavell RA ( Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.); Gaspari AA ( 1] Department of Dermatology, University of Maryland, Baltimore, Maryland, USA [2] Department of Microbiology/Immunology, University of Maryland, Baltimore, Maryland, USA.) |
| 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. |
