title: A T(h)17-polarized cell population that has infiltrated the lung requires cells that convert to IFN-{gamma} production in order to induce airway hyperresponsiveness.
abstract: Adoptive cell transfer of an ovalbumin (OVA)-specific T(h)17-polarized cell population from transgenic DO11.10 mice into BALB/c mice followed by OVA inhalation caused airway hyperresponsiveness (AHR) with severe neutrophilia. The transferred T(h)17 cell population-previously polarized in vitro with IL-6, transforming growth factor-beta and IL-23-contained negligible numbers of IFN-gamma-producing cells; however, during T(h)17-cell-dependent airway inflammation, significant numbers of IFN-gamma-producing cells-including cells producing both IL-17 and IFN-gamma and cells producing only IFN-gamma-were detected in the lung in addition to cells producing only IL-17. Using T(h)17-polarized cell populations derived from IL-17(-/-) or IFN-gamma(-/-) mice, it was demonstrated that IL-17 is essential for inducing neutrophilic airway inflammation and that IFN-gamma is required for the AHR elevation. IFN-gamma appeared to be derived from cells producing both IL-17 and IFN-gamma and/or from cells producing only IFN-gamma, which were converted from the transferred T(h)17-polarized cell population. We also found that mAbs that neutralize IL-12 significantly suppressed the conversion of the T(h)17-polarized cell population toward IFN-gamma producers in the lung; concomitantly, with this decreased conversion, IL-12 neutralization also attenuated the AHR elevation in the lung. IL-12-dependent conversion of the transferred T(h)17-polarized cell population into IFN-gamma producers in the lung thus appeared to be a crucial process for inducing AHR elevation in T(h)17-cell-dependent airway inflammation.
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ashino
authors.forename: Daiko
authors.initials: D
authors.lastname: Wakita
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shiohama
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Kenji
authors.initials: K
authors.lastname: Chamoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ohkuri
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Kitamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishimura
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D019138:Antibodies, Blocking; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D002465:Cell Movement; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009504:Neutrophils / Q000473:pathology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D019138:Antibodies, Blocking; D020381:Interleukin-17; D011948:Receptors, Antigen, T-Cell; D018664:Interleukin-12; D007371:Interferon-gamma; D010047:Ovalbumin