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.
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Acknowledgements
We thank J.N. Ihle (St. Jude Children's Research Hospital) for providing Tslpr−/− mice, and H. Sage and G. Nepom for critical reading of the manuscript. Supported by the National Institutes of Health (AI44259 to S.F.Z.) and the American Lung Association of Washington (B.Z.).
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M.R.C. and T.D.S. are employees of Amgen.
Supplementary information
Supplementary Fig. 1
Alveolar macrophages from Tslpr−/− mice, sensitized and challenged with OVA, are less activated than those from Tslpr+/+ mice. (PDF 903 kb)
Supplementary Fig. 2
The SPC-Tslpr-transgenic mice showed no obvious abnormalities in the development of immune system at 2-3 months of age when lung showed fully asthma-like phenotypes. (PDF 752 kb)
Supplementary Fig. 3
CD4+ T cells in the BAL of SPC-Tslpr-mice increased CCR4 expression while losing lymph node homing receptors CD62L and CCR7. (PDF 149 kb)
Supplementary Fig. 4
Normal littermate control (NLC) mice showed no signs of airway remodeling. (PDF 917 kb)
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Zhou, B., Comeau, M., Smedt, T. et al. Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice. Nat Immunol 6, 1047–1053 (2005). https://doi.org/10.1038/ni1247
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DOI: https://doi.org/10.1038/ni1247
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