title: Identification of an IL-17-producing NK1.1(neg) iNKT cell population involved in airway neutrophilia.
abstract: Invariant natural killer T (iNKT) cells are an important source of both T helper type 1 (Th1) and Th2 cytokines, through which they can exert beneficial, as well as deleterious, effects in a variety of inflammatory diseases. This functional heterogeneity raises the question of how far phenotypically distinct subpopulations are responsible for such contrasting activities. In this study, we identify a particular set of iNKT cells that lack the NK1.1 marker (NK1.1(neg)) and secrete high amounts of interleukin (IL)-17 and low levels of interferon (IFN)-gamma and IL-4. NK1.1(neg) iNKT cells produce IL-17 upon synthetic (alpha-galactosylceramide [alpha-GalCer] or PBS-57), as well as natural (lipopolysaccharides or glycolipids derived from Sphingomonas wittichii and Borrelia burgdorferi), ligand stimulation. NK1.1(neg) iNKT cells are more frequent in the lung, which is consistent with a role in the natural immunity to inhaled antigens. Indeed, airway neutrophilia induced by alpha-GalCer or lipopolysaccharide instillation was significantly reduced in iNKT-cell-deficient Jalpha18(-/-) mice, which produced significantly less IL-17 in their bronchoalveolar lavage fluid than wild-type controls. Furthermore, airway neutrophilia was abolished by a single treatment with neutralizing monoclonal antibody against IL-17 before alpha-GalCer administration. Collectively, our findings reveal that NK1.1(neg) iNKT lymphocytes represent a new population of IL-17-producing cells that can contribute to neutrophil recruitment through preferential IL-17 secretion.
authors.affiliation: Unité Mixte de Recherche 8147, Centre National de la Recherche Scientifique, Faculté de Médecine René Descartes, Paris V, Hôpital Necker, Paris, Cedex 15, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Michel
authors.forename: Alexandre Castro
authors.initials: AC
authors.lastname: Keller
authors.forename: Christophe
authors.initials: C
authors.lastname: Paget
authors.forename: Masakazu
authors.initials: M
authors.lastname: Fujio
authors.forename: François
authors.initials: F
authors.lastname: Trottein
authors.forename: Paul B
authors.initials: PB
authors.lastname: Savage
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
authors.forename: Elke
authors.initials: E
authors.lastname: Schneider
authors.forename: Michel
authors.initials: M
authors.lastname: Dy
authors.forename: Maria C
authors.initials: MC
authors.lastname: Leite-de-Moraes
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000235:genetics; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D005699:Galactosylceramides; D006017:Glycolipids; D020381:Interleukin-17 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics; D008168:Lung / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B; D020556:Neutrophil Infiltration / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D000954:Antigens, Surface; D005699:Galactosylceramides; D006017:Glycolipids; D020381:Interleukin-17; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; C512575:PBS 57; C493154:alpha-galactosylceramide