IL-9 Regulates Allergen-Specific Th1 Responses in Allergic Contact Dermatitis

• Published in: Journal of investigative dermatology Vol. 134; no. 7; pp. 1903 - 1911
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2014; Elsevier Limited
• Subjects: 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
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/jid.2014.61

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.