A natural protective function of invariant NKT cells in a mouse model of innate-cell-driven lung inflammation

✍ Scribed by Elvire A. Bourgeois; Anaïs Levescot; Séverine Diem; Angélique Chauvineau; Hortense Bergès; Pierre Milpied; Agnès Lehuen; Diane Damotte; Jean-Marc Gombert; Elke Schneider; Jean-Philippe Girard; Pierre Gourdy; André Herbelin

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 258 KB
• Volume: 41
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.201040647

✦ Synopsis

Activation of invariant natural killer T (iNKT) cells by treatment with their a-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 (Ja18 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 Ja18 KO mice. Finally, we established that this natural anti-inflammatory function of iNKT cells depends on their IFN-c 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.