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-gamma, 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 alpha-galactosylceramide (alpha-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-gamma-producing NKT cells. IL-17-producing NKT cells showed unresponsiveness after stimulation of alpha-GalCer as conventional NKT cells. During airway inflammation induced by pulmonary activation of NKT cells with alpha-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.
Lee
Kyoo-A
KA
Laboratory of Immunology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shillim-dong, Kwanak-gu, Seoul 151-742, Republic of Korea.
Kang
Min-Hee
MH
Lee
Yoon-Sook
YS
Kim
Yeon-Jeong
YJ
Kim
Dong-Hyeon
DH
Ko
Hyun-Jeong
HJ
Kang
Chang-Yuil
CY
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D018893:Bronchoalveolar Lavage; D005260:Female; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000494:pharmacology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D012313:RNA / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D005699:Galactosylceramides; D020381:Interleukin-17; D011948:Receptors, Antigen, T-Cell; C493154:alpha-galactosylceramide; D012313:RNA