Abstract
The cytokine thymic stromal lymphopoietin (TSLP) has been linked to human allergic inflammatory diseases. We show here that TSLP expression was increased in the lungs of mice with antigen-induced asthma, whereas TSLP receptor-deficient mice had considerably attenuated disease. Lung-specific expression of a Tslp transgene induced airway inflammation and hyperreactivity characterized by T helper type 2 cytokines and increased immunoglobulin E. The lungs of Tslp-transgenic mice showed massive infiltration of leukocytes, goblet cell hyperplasia and subepithelial fibrosis. TSLP was capable of activating bone marrow-derived dendritic cells to upregulate costimulatory molecules and produce the T helper type 2 cell-attracting chemokine CCL17. These findings suggest that TSLP is an important factor necessary and sufficient for the initiation of allergic airway inflammation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Allergens / adverse effects
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Animals
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Asthma / etiology
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Asthma / immunology*
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Asthma / pathology
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Chemokine CCL17
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Chemokines, CC / biosynthesis
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Cytokines / metabolism
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Cytokines / physiology*
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Dendritic Cells / immunology
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Disease Models, Animal
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Goblet Cells / pathology
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Hyperplasia / pathology
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Immunoglobulins
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Inflammation / pathology
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Leukocytes / pathology
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Lung / metabolism
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Lung / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Ovalbumin / adverse effects
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Pulmonary Fibrosis / pathology
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Receptors, Cytokine / deficiency
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Receptors, Cytokine / genetics
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Thymic Stromal Lymphopoietin
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Up-Regulation
Substances
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Allergens
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Ccl17 protein, mouse
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Chemokine CCL17
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Chemokines, CC
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Cytokines
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Immunoglobulins
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Receptors, Cytokine
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Tslpr protein, mouse
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Ovalbumin
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Thymic Stromal Lymphopoietin
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TSLP protein, mouse