A novel subset of mouse NKT cells bearing the IL-17 receptor B responds to IL-25 and contributes to airway hyperreactivity.
Airway hypersensitive reaction (AHR) is an animal model for asthma, which is caused or enhanced by environmental factors such as allergen exposure. However, the precise mechanisms that drive AHR remain unclear. We identified a novel subset of natural killer T (NKT) cells that expresses the interleukin 17 receptor B (IL-17RB) for IL-25 (also known as IL-17E) and is essential for the induction of AHR. IL-17RB is preferentially expressed on a fraction of CD4(+) NKT cells but not on other splenic leukocyte populations tested. IL-17RB(+) CD4(+) NKT cells produce predominantly IL-13 and Th2 chemokines upon stimulation with IL-25 in vitro. IL-17RB(+) NKT cells were detected in the lung, and depletion of IL-17RB(+) NKT cells by IL-17RB-specific monoclonal antibodies or NKT cell-deficient Jalpha18(-/-) mice failed to develop IL-25-dependent AHR. Cell transfer of IL-17RB(+) but not IL-17RB(-) NKT cells into Jalpha18(-/-) mice also successfully reconstituted AHR induction. These results strongly suggest that IL-17RB(+) CD4(+) NKT cells play a crucial role in the pathogenesis of asthma.
Terashima
Asuka
A
Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan.
Watarai
Hiroshi
H
Inoue
Sayo
S
Sekine
Etsuko
E
Nakagawa
Ryusuke
R
Hase
Koji
K
Iwamura
Chiaki
C
Nakajima
Hiroshi
H
Nakayama
Toshinori
T
Taniguchi
Masaru
M
D000818:Animals; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007144:Immunoglobulin J-Chains / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D010641:Phenotype; D053722:Receptors, Interleukin-17 / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016207:Cytokines; D007144:Immunoglobulin J-Chains; D007378:Interleukins; C442281:Mydgf protein, mouse; D053722:Receptors, Interleukin-17; D010047:Ovalbumin