Nature Immunology
6, 1047 - 1053 (2005)
Published online: 4 September 2005; | doi:10.1038/ni1247
Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in miceBaohua Zhou1, Michael R Comeau3, Thibaut De Smedt3, H Denny Liggitt4, Martin E Dahl5, David B Lewis5, Dora Gyarmati1, Theingi Aye1, Daniel J Campbell1, 2
& Steven F Ziegler1, 21
Immunology Program, Benaroya Research Institute, Seattle, Washington 98101, USA. 2
Department of Immunology, University of Washington School of Medicine, Seattle, Washington 98195, USA. 3
Immune Regulation Group, Amgen, Seattle, Washington 98119, USA. 4
Department of Comparative Medicine, University of Washington School of Medicine, Seattle, Washington 98195, USA. 5
Department of Pediatrics and the Immunology Program, Stanford University School of Medicine, Stanford, California 94305, USA.
Correspondence should be addressed to Steven F Ziegler sziegler@benaroyaresearch.org 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.
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