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Am J Respir Crit Care Med. 2014 Dec 15;190(12):1373-82. doi: 10.1164/rccm.201406-1039OC.

IL-33-dependent type 2 inflammation during rhinovirus-induced asthma exacerbations in vivo.

Author information

1
1 Airway Disease Infection Section, National Heart & Lung Institute, Imperial College London, London, United Kingdom.

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.

KEYWORDS:

ILC2; Th2; infection; virus

PMID:
25350863
PMCID:
PMC4299647
DOI:
10.1164/rccm.201406-1039OC
[Indexed for MEDLINE]
Free PMC Article

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