Plasmacytoid dendritic cells drive acute exacerbations of asthma
File(s)
Author(s)
Type
Journal Article
Abstract
BACKGROUND: Although acute exacerbations, mostly triggered by viruses, account for the majority of hospitalizations in asthma, there is still very little known about the pathophysiological mechanisms involved. Plasmacytoid DCs (pDCs), prominent cells of antiviral immunity, exhibit pro-inflammatory or tolerogenic functions depending on the context, yet their involvement in asthma exacerbations remains unexplored. OBJECTIVES: We sought to investigate the role of pDCs in allergic airway inflammation and acute exacerbations of asthma. METHODS: Animal models of allergic airway disease (AAD) and virus-induced AAD exacerbations were employed to dissect pDC function in vivo and unwind potential mechanisms involved. Sputum from asthma patients with stable disease or acute exacerbations was further studied to determine pDC presence and correlation with inflammation. RESULTS: pDCs were key mediators of the immuno-inflammatory cascade that drives asthma exacerbations. In animal models of AAD and RV-induced AAD exacerbations, pDCs were recruited to the lung during inflammation and migrated to the draining lymph nodes to boost Th2-mediated effector responses. Accordingly, pDC depletion post-allergen challenge or during RV infection abrogated exacerbation of inflammation and disease. Central to this process was IL-25, induced by allergen challenge or RV infection that conditioned pDCs for pro-inflammatory function. Consistently, in asthma patients pDCs were markedly increased during exacerbations, and correlated with the severity of inflammation and the risk for asthmatic attacks. CONCLUSIONS: Our studies uncover a previously unsuspected role of pDCs in asthma exacerbations with potential diagnostic and prognostic implications. They also propose the therapeutic targeting of pDCs and IL-25 for the treatment of acute asthma.
Date Issued
2018-08-01
Date Acceptance
2017-08-23
Citation
Journal of Allergy and Clinical Immunology, 2018, 142 (2), pp.542-556.e12
ISSN
0091-6749
Publisher
Elsevier
Start Page
542
End Page
556.e12
Journal / Book Title
Journal of Allergy and Clinical Immunology
Volume
142
Issue
2
Copyright Statement
© 2017, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor
Commission of the European Communities
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
National Institute for Health Research
Identifier
PII: S0091-6749(17)31586-5
Grant Number
260895
G1000758
G1100168
G1000758
NF-SI-0514-10092
Subjects
Plasmacytoid dendritic cells
animal models of allergic airway disease
asthma
asthma exacerbations
rhinovirus
Publication Status
Published
Date Publish Online
2017-10-17