T H 2 and T H 17 inflammatory pathways are reciprocally regulated in asthma
| العنوان: | T H 2 and T H 17 inflammatory pathways are reciprocally regulated in asthma |
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| المؤلفون: | Janet Jackman, Emma Doran, Jackson G. Egen, Peter Bradding, Chandra M. Ohri, Kevin M. Hart, Joshua Sciurba, Lawren C. Wu, Thirumalai R. Ramalingam, Robert W. Thompson, Kevin M. Vannella, Joseph R. Arron, Thomas A. Wynn, Lee A. Borthwick, Claire A. Butler, Deepti R. Nagarkar, Aarti Shikotra, Beverley Hargadon, Liam G Heaney, Salman Siddiqui, Guiquan Jia, Sandra White, Alexander R. Abbas, David F. Choy, Richard L. Gieseck |
| المصدر: | Science Translational Medicine. 7 |
| بيانات النشر: | American Association for the Advancement of Science (AAAS), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Cytokine Suppression, business.industry, General Medicine, Hyperplasia, medicine.disease, Mucus, Interleukin 13, Immunology, Medicine, Eosinophilia, Interleukin 17, medicine.symptom, Signal transduction, business, Asthma |
| الوصف: | Increasing evidence suggests that asthma is a heterogeneous disorder regulated by distinct molecular mechanisms. In a cross-sectional study of asthmatics of varying severity (n = 51), endobronchial tissue gene expression analysis revealed three major patient clusters: TH2-high, TH17-high, and TH2/17-low. TH2-high and TH17-high patterns were mutually exclusive in individual patient samples, and their gene signatures were inversely correlated and differentially regulated by interleukin-13 (IL-13) and IL-17A. To understand this dichotomous pattern of T helper 2 (TH2) and TH17 signatures, we investigated the potential of type 2 cytokine suppression in promoting TH17 responses in a preclinical model of allergen-induced asthma. Neutralization of IL-4 and/or IL-13 resulted in increased TH17 cells and neutrophilic inflammation in the lung. However, neutralization of IL-13 and IL-17 protected mice from eosinophilia, mucus hyperplasia, and airway hyperreactivity and abolished the neutrophilic inflammation, suggesting that combination therapies targeting both pathways may maximize therapeutic efficacy across a patient population comprising both TH2 and TH17 endotypes. |
| تدمد: | 1946-6242 1946-6234 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::a0fc78b77210426a2921fbba37bc657d https://doi.org/10.1126/scitranslmed.aab3142 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........a0fc78b77210426a2921fbba37bc657d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19466242 19466234 |
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