Jackson, DJ, Makrinioti, H, Rana, BMJ, Shamji, BWH, Trujillo-Torralbo, MB, Footitt, J, Del-Rosario, J, Telcian, AG, Nikonova, A, Zhu, J, Aniscenko, J, Gogsadze, L, Bakhsoliani, E, Traub, S, Dhariwal, J, Porter, J, Hunt, D, Hunt, T, Hunt, T, Stanciu, LA, Khaitov, M, Bartlett, NW, Edwards, MR, Kon, OM, Mallia, P, Papadopoulos, NG, Akdis, CA, Westwick, J, Edwards, MJ, Cousins, DJ, Walton, RP and Johnston, SL (2014) IL-33-Dependent Type 2 Inflammation during Rhinovirus-induced Asthma Exacerbations In Vivo. American Journal of Respiratory and Critical Care Medicine. 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

Item Type:	Article
Additional Information:	NIBR author: Shamji, BWH institute: NIBR contributor address: Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Airway Dis Infect Sect, London W2 1PG, England, MRC, London, England, Asthma UK Ctr Allerg Mech Asthma, London, England, Imperial Coll Healthcare NHS Trust, London, England s.johnston@imperial.ac.uk; Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Airway Dis Infect Sect, London W2 1PG, England, MRC, London, England, Asthma UK Ctr Allerg Mech Asthma, London, England ; MRC, London, England, Asthma UK Ctr Allerg Mech Asthma, London, England ; Kings Coll London, Div Asthma Allergy & Lung Biol, London, England, Novartis Inst Biomed Res, Horsham, W Sussex, England ; Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Airway Dis Infect Sect, London W2 1PG, England, MRC, London, England, Asthma UK Ctr Allerg Mech Asthma, London, England, Natl Res Ctr, Inst Immunol, Fed Med & Biol Agcy Russian Federat FMBA, Moscow, Russia ; Hunt Dev UK Ltd, Midhurst, England ; Natl Res Ctr, Inst Immunol, Fed Med & Biol Agcy Russian Federat FMBA, Moscow, Russia ; Imperial Coll Healthcare NHS Trust, London, England ; Attikon Gen Univ Hosp, Allergy Unit, Athens, Greece ; Univ Zurich, Swiss Inst Allergy & Asthma Res, Davos, Switzerland ; Novartis Inst Biomed Res, Horsham, W Sussex, England ; MRC, London, England, Asthma UK Ctr Allerg Mech Asthma, London, England, Kings Coll London, Div Asthma Allergy & Lung Biol, London, England ; Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Airway Dis Infect Sect, London W2 1PG, England; MRC, London, England; Asthma UK Ctr Allerg Mech Asthma, London, England; Imperial Coll Healthcare NHS Trust, London, England; Johnston, S L; Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Airway Dis Infect Sect, Norfolk Pl, London W2 1PG, England
Date Deposited:	13 Oct 2015 13:11
Last Modified:	13 Oct 2015 13:11
URI:	https://oak.novartis.com/id/eprint/24932