A distinct subset of natural killer T cells produces IL-17, contributing to airway infiltration of neutrophils but not to airway hyperreactivity

Activated natural killer T (NKT) cells produce a broad range of cytokines, including IL-4 and IFN-γ, that determine immunomodulatory functions in various animal models. In this report, we show that a well-known proinflammatory cytokine, IL-17 is also produced by a distinct population of NKT cells upon TCR stimulation. Administration of α-galactosylceramide (α-GalCer), a strong agonist of NKT cells, induces rapid IL-17 production by a small population of NKT cells, mostly belonging to a population different from that of IL-4- and IFN-γ-producing NKT cells. IL-17-producing NKT cells showed unresponsiveness after stimulation of α-GalCer as conventional NKT cells. During airway inflammation induced by pulmonary activation of NKT cells with α-GalCer, IL-17 contributes to the infiltration of neutrophils into the airway but has no effect on airway hyperreactivity (AHR). These results indicate that TCR stimulation induces IL-17 expression by a novel population of NKT cells and may help to explain diverse NKT cell functions.