1. A natural protective function of invariant NKT cells in a mouse model of innate-cell-driven lung inflammation.
- Author
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Bourgeois EA, Levescot A, Diem S, Chauvineau A, Bergès H, Milpied P, Lehuen A, Damotte D, Gombert JM, Schneider E, Girard JP, Gourdy P, and Herbelin A
- Subjects
- Adoptive Transfer, Animals, Bronchitis blood, Bronchitis chemically induced, Bronchoalveolar Lavage Fluid chemistry, Cell Count, Chemokines blood, Chemokines metabolism, DNA-Binding Proteins genetics, Disease Models, Animal, Eosinophils pathology, Female, Interferon-gamma genetics, Interferon-gamma metabolism, Interleukin-12 genetics, Interleukin-12 metabolism, Interleukin-33, Interleukin-5 blood, Interleukins pharmacology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Natural Killer T-Cells metabolism, Natural Killer T-Cells transplantation, Neutrophils pathology, Receptors, Antigen, T-Cell, alpha-beta genetics, Recombinant Proteins pharmacology, Bronchitis immunology, Bronchitis pathology, Immunity, Innate immunology, Natural Killer T-Cells immunology
- Abstract
Activation of invariant natural killer T (iNKT) cells by treatment with their α-galactosyl ceramide ligand provides therapeutic benefits in several immune inflammatory settings. Given the artificial nature of this stimulation, the natural regulatory functions of iNKT remain uncertain. Addressing this issue in a mouse model of innate-cell-driven lung inflammation induced by the cytokine/alarmin IL-33 that targets iNKT cells, we found that eosinophil and neutrophil recruitment was markedly increased in treated iNKT cell-deficient (Jα18 KO) mice, as was the local production of eotaxin and keratinocyte chemoattractant chemokines. By contrast, lung inflammation decreased after adoptive transfer of iNKT cells, which restored the WT inflammatory response in Jα18 KO mice. Finally, we established that this natural anti-inflammatory function of iNKT cells depends on their IFN-γ production and on endogenous IL-12. Our study provides the first evidence of a protective role of iNKT cells during lung inflammation that does not require pharmacological TCR engagement., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2011
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