Identification of an IL-17–producing NK1.1neg iNKT cell population involved in airway neutrophilia

By Marie‐Laure Michel, A. Keller, C. Paget, M. Fujio, F. Trottein, P. Savage, Chi‐Huey Wong, E. Schneider, M. Dy, M. Leite-de-Moraes. Journal of Experimental Medicine, 2007

647 citations recorded by the source corpus.

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)-γ and IL-4. NK1.1neg iNKT cells produce IL-17 upon synthetic (α-galactosylceramide [α-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 α-GalCer or lipopolysaccharide instillation was significantly reduced in iNKT-cell–deficient Jα18−/− 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 α-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.

Subfields: Emergency Medical Services, Immunology

View Paper: https://www.semanticscholar.org/paper/622114d3245af59d0c78a8bc37d1fb476b7231aa

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Citations in the corpus

Innate IL-17-producing cells: the sentinels of the immune system (2010, background): “Additional innate IL-17-producing cells described in the literature include CD3 + invariant natural killer T (iNKT) cells , lymphoid-tissue inducer (LTi)-like cells, natural killer (NK) cells and myeloid cell”
Raising the NKT cell family (2010, background): “A newly identified subset of NKT cells produces very high concentrations of the proinflammatory cytokine IL-17 within 2–3 hour of stimulatio”
Fate mapping of interleukin 17-producing T cells in inflammatory responses (2011, background): “Thus, IL-17-producing cells, including innate γδ T cells and natural killer T cell”
Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals. (2009, neutral): “Among these, natural killer T (NKT) cells (Michel et al., 2007) and gd T cells (Roark et al., 2008) have been shown to be potent sources of IL-17 and, in some cases, more dominant than Th17 CD4+ T cells.”