Differential role of thymic stromal lymphopoietin in the induction of airway hyperreactivity and Th2 immune response in antigen-induced asthma with respect to natural killer T cell function.
Asthma is an inflammatory lung disease, in which CD1d-restricted natural killer T (NKT) cells play an important pathogenic role. Also, recent reports indicated that a cytokine, thymic stromal lymphopoietin (TSLP), is essential for the development of antigen-induced asthma. Here we examined the relationship between NKT cells and TSLP in a mouse model of asthma. NKT cells express TSLP receptor as well as IL-7 receptor alpha-chain. TSLP acts on NKT cells to preferentially increase their IL-13 production but not IFN-gamma and IL-4. In an allergen-induced asthma model, the development of airway hyperreactivity, a cardinal feature of asthma, was increased in TSLP transgenic mice, whereas this effect was not observed in TSLP transgenic mice lacking NKT cells. Interestingly, in the NKT cell-lacking TSLP transgenic mice, pulmonary eosinophilia and increase in IgE did not improve. Pulmonary lymphocytes from the NKT cell-lacking TSLP transgenic mice produced much less IL-13 upon CD3 stimulation than those from NKT cell-competent TSLP transgenic mice. These resultssuggest that, in allergen-induced asthma, TSLP acts on NKT cells to enhance airway hyperreactivity by upregulating their IL-13 production, whereas eosinophilia and IgE production are not influenced.
Nagata
Yuko
Y
Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan.
Kamijuku
Hajime
H
Taniguchi
Masaru
M
Ziegler
Steven
S
Seino
Ken-ichiro
K
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007136:Immunoglobulins; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D018418:Th2 Cells / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D007136:Immunoglobulins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D011994:Recombinant Proteins; C410591:Tslpr protein, mouse; D007073:Immunoglobulin E; D010047:Ovalbumin; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse