title: Allergen-Induced IL-6 Regulates IL-9/IL-17A Balance in CD4+ T Cells in Allergic Airway Inflammation.
abstract: IL-9-secreting Th9 cells have been considered to play a pivotal role in the pathogenesis of atopic diseases. To what extent IL-9-producing cells are induced or regulated by sensitization with naturally occurring allergens is not yet clear. Naturally occurring allergens are capable of inducing IL-6 production in dendritic cells (DCs). Whether allergen-induced IL-6 supports a Th9 subtype by increasing IL-9 production, as observed in in vitro studies, or rather favors Th17 differentiation is not finally resolved. Therefore, in the present study we have investigated the impact of IL-6 on the Th9/Th17 balance depending on the predominant cytokine milieu and, additionally, in vivo using a DC-driven murine asthma model. In vitro, IL-6 increases Th9 cells under strong IL-4 and TGF-β activation, whereas under moderate IL-4 and TGF-β activation the presence of IL-6 shifts naive CD4(+) cells to Th17 cells. To induce allergic airway inflammation, OVA-pulsed DCs from IL-6-deficient or wild-type donors were adoptively transferred into BALB/c mice. Recipients receiving IL-6-producing wild-type DCs showed a significant decrease of Th9- and IL-4-producing Th2 cells but an increase of Th17 cells in lung tissue in comparison with recipients sensitized with IL-6-deficient DCs. Our data suggest that the IL-6-mediated reduction of Th2-related IL-4 leads to a decline of the Th9 immune response and allows Th17 differentiation.
authors: Leipzig Research Center for Civilization Diseases, Junior Research Group on Pathogenesis of New Allergies, Leipzig University Medical Center, 04103 Leipzig, Germany; Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, 04103 Leipzig, Germany; nicole.schuetze@vetmed.uni-leipzig.de.
authors: Nicole
authors: N
authors: Schütze
authors: Leipzig Research Center for Civilization Diseases, Junior Research Group on Pathogenesis of New Allergies, Leipzig University Medical Center, 04103 Leipzig, Germany; Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, 04103 Leipzig, Germany;
authors: Stefanie
authors: S
authors: Trojandt
authors: Department of Environmental Immunology, UFZ-Helmholtz Center for Environmental Research, 04318 Leipzig, Germany;
authors: Stephanie
authors: S
authors: Kuhn
authors: Department of Proteomics, UFZ-Helmholtz Center for Environmental Research, 04318 Leipzig, Germany;
authors: Janina M
authors: JM
authors: Tomm
authors: Department of Proteomics, UFZ-Helmholtz Center for Environmental Research, 04318 Leipzig, Germany; Department of Metabolomics, UFZ-Helmholtz Center for Environmental Research, 04318 Leipzig, Germany; and Department of Chemistry and Bioscience, Aalborg University, 9220 Aalborg, Denmark.
authors: Martin
authors: M
authors: von Bergen
authors: Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, 04103 Leipzig, Germany;
authors: Jan C
authors: JC
authors: Simon
authors: Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, 04103 Leipzig, Germany; Department of Environmental Immunology, UFZ-Helmholtz Center for Environmental Research, 04318 Leipzig, Germany;
authors: Tobias
authors: T
authors: Polte
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology*; D016906:Interleukin-9 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000485:Allergens; D020381:Interleukin-17; D015850:Interleukin-6; D016906:Interleukin-9