Please use this identifier to cite or link to this item:
|Title:||Th2 and Th17 inflammatory pathways are reciprocally regulated in asthma|
|Authors:||Choy, D. F.|
Hart, K. M.
Borthwick, L. A.
Nagarkar, D. R.
Ohri, Chandra M.
Vannella, K. M.
Butler, C. A.
Sciurba, J. C.
Gieseck, R. L.
Thompson, R. W.
Abbas, A. R.
Wu, L. C.
Egen, J. G.
Heaney, L. G.
Ramalingam, T. R.
Arron, J. R.
Wynn, T. A.
|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.|
|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|
Files in This Item:
|TH2_17_STMFINAL accepted version.pdf||Post-review (final submitted)||11.62 MB||Adobe PDF||View/Open|
|TH2_17_STMFINAL+accepted+version.pdf||Post-review (final submitted)||11.62 MB||Adobe PDF||View/Open|
Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.