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Title: IL-33-dependent type 2 inflammation during rhinovirus-induced asthma exacerbations in vivo
Authors: Jackson, David J.
Makrinioti, Heidi
Rana, Batika M. J.
Shamji, Betty W. H.
Trujillo-Torralbo, Maria-Belen
Footitt, Joseph
del-Rosario, Jerico
Telcian, Aurica G.
Nikonova, Alexandra
Zhu, Jie
Aniscenko, Julia
Gogsadze, Leila
Bakhsoliani, Eteri
Traub, Stephanie
Dhariwal, Jaideep
Porter, James
Hunt, Duncan
Hunt, Toby
Hunt, Trevor
Stanciu, Luminita A.
Khaitov, Musa
Bartlett, Nathan W.
Edwards, Michael R.
Kon, Onn Min
Mallia, Patrick
Papadopoulos, Nikolaos G.
Akdis, Cezmi A.
Westwick, John
Edwards, Matthew J.
Cousins, David J.
Walton, Ross P.
Johnston, Sebastian L.
First Published: 15-Dec-2014
Publisher: American Thoracic Society
Citation: American Journal of Respiratory and Critical Care Medicine, 190 (12), 2014, pp. 1373-1382.
Abstract: Rationale: Rhinoviruses are the major cause of asthma exacerbations; however, its underlying mechanisms are poorly understood. We hypothesized that the epithelial cell–derived cytokine IL-33 plays a central role in exacerbation pathogenesis through augmentation of type 2 inflammation. Objectives: To assess whether rhinovirus induces a type 2 inflammatory response in asthma in vivo and to define a role for IL-33 in this pathway. Methods: We used a human experimental model of rhinovirus infection and novel airway sampling techniques to measure IL-4, IL-5, IL-13, and IL-33 levels in the asthmatic and healthy airways during a rhinovirus infection. Additionally, we cultured human T cells and type 2 innate lymphoid cells (ILC2s) with the supernatants of rhinovirus- infected bronchial epithelial cells (BECs) to assess type 2 cytokine production in the presence or absence of IL-33 receptor blockade. Measurements and Main Results: IL-4, IL-5, IL-13, and IL-33 are all induced by rhinovirus in the asthmatic airway in vivo and relate to exacerbation severity. Further, induction of IL-33 correlates with viral load and IL-5 and IL-13 levels. Rhinovirus infection of human primary BECs induced IL-33, and culture of human T cells and ILC2s with supernatants of rhinovirus-infected BECs strongly induced type 2 cytokines. This induction was entirely dependent on IL-33. Conclusions: IL-33 and type 2 cytokines are induced during a rhinovirus-induced asthma exacerbation in vivo. Virus-induced IL-33 and IL-33 – responsive T cells and ILC2s are key mechanistic links between viral infection and exacerbation of asthma. IL-33 inhibition is a novel therapeutic approach for asthma exacerbations.
DOI Link: 10.1164/rccm.201406-1039OC
ISSN: 1073-449X
eISSN: 1535-4970
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2014, American Thoracic Society. Deposited with reference to the publisher’s archiving policy available on the SHERPA/RoMEO website.
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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