Identification of an IL-17-producing NK1.1(neg) iNKT cell population involved in airway neutrophilia.
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.
Michel
Marie-Laure
ML
Unité Mixte de Recherche 8147, Centre National de la Recherche Scientifique, Faculté de Médecine René Descartes, Paris V, Hôpital Necker, Paris, Cedex 15, France.
Keller
Alexandre Castro
AC
Paget
Christophe
C
Fujio
Masakazu
M
Trottein
François
F
Savage
Paul B
PB
Wong
Chi-Huey
CH
Schneider
Elke
E
Dy
Michel
M
Leite-de-Moraes
Maria C
MC
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*
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