Keywords
cells, inflammatory disease, cell population, 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 (NK1.1neg) and secrete high amounts of interleukin (IL)-17 and low levels of interferon (IFN)-{gamma} and IL-4. NK1.1neg 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. NK1.1neg 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 J{alpha}18-/- 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 NK1.1neg iNKT lymphocytes represent a new population of IL-17-producing cells that can contribute to neutrophil recruitment through preferential IL-17 secretion.
Original Publication Citation
Michel, M. L., A. C. Keller, C. Paget, M. Fujio, F. Trottein, P. B. Savage, C.-H. Wong, E. Schneider, M. Dy, and M. C. Leite-De-Moraes (27, April). Identification of an il-17-producing nk1.1neg inkt cell population involved in airway neutrophilia. J. Exp. Med. , jem.261551+.
BYU ScholarsArchive Citation
Savage, Paul B.; Michel, Marie-Laure; Keller, Alexandre Castro; Paget, Christophe; Fujio, Masakazu; Trottein, Francois; Wong, Chi-Huey; Schneider, Elke; Dy, Michael; and Leite-de-Moraes, Maria C., "Identification of an IL-17-producing NK1.1neg iNKT cell population involved in airway neutrophilia" (2004). Faculty Publications. 441.
https://scholarsarchive.byu.edu/facpub/441
Document Type
Peer-Reviewed Article
Publication Date
2004-04-30
Permanent URL
http://hdl.lib.byu.edu/1877/1484
Publisher
The Rockefeller University Press
Language
English
College
Physical and Mathematical Sciences
Department
Chemistry and Biochemistry
Copyright Status
© 2007 Michel et al.
Copyright Use Information
http://lib.byu.edu/about/copyright/