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Title: Th2 and Th17 inflammatory pathways are reciprocally regulated in asthma
Authors: Choy, D. F.
Hart, K. M.
Borthwick, L. A.
Shikotra, Aarti
Nagarkar, D. R.
Siddiqui, Salman
Jia, G.
Ohri, Chandra M.
Doran, E.
Vannella, K. M.
Butler, C. A.
Hargadon, Beverley
Sciurba, J. C.
Gieseck, R. L.
Thompson, R. W.
White, S.
Abbas, A. R.
Jackman, J.
Wu, L. C.
Egen, J. G.
Heaney, L. G.
Ramalingam, T. R.
Arron, J. R.
Wynn, T. A.
Bradding, Peter
First Published: 19-Aug-2015
Publisher: American Association for the Advancement of Science
Citation: Science Translational Medicine 19 Aug 2015: Vol. 7, Issue 301, pp. 301ra129
Abstract: Increasing evidence suggests that asthma is a heterogeneous disorder regulated by distinct molecular mechanisms. Here, 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/Th17-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 IL-13 and IL-17A. To understand this dichotomous pattern of 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-1 and IL-17 protected subjects from eosinophilia, mucus hyperplasia, 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.
DOI Link: 10.1126/scitranslmed.aab3142
ISSN: 1946-6234
eISSN: 1946-6242
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science Translational Medicine on 19 Aug 2015: Vol. 7, DOI: 10.1126/scitranslmed.aab3142
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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