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  4. Mucosal type 2 innate lymphoid cells are a key component of the allergic response to aeroallergen
 
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Mucosal type 2 innate lymphoid cells are a key component of the allergic response to aeroallergen
File(s)
Mucosal type 2 innate lymphoid cells identified as central to the allergic response in asthma 091216.docx (11.94 MB)
Accepted version
Author(s)
Dhariwal, J
Cameron, A
Trujillo-Torralbo, MB
Del Rosario, A
Bakhsoliani, E
more
Type
Journal Article
Abstract
RATIONALE: Newly characterised type 2 innate lymphoid cells display potent type 2 effector functionality, however their contribution to allergic airways inflammation and asthma is poorly understood. Mucosal biopsy used to characterise the airway mucosa is invasive, poorly tolerated and does not allow sequential sampling. OBJECTIVES: To assess the role of type 2 innate lymphoid cells during nasal allergen challenge in subjects with allergic rhinitis, using novel non-invasive methodology. METHODS: We used a human experimental allergen challenge model, with flow cytometric analysis of nasal curettage samples, to assess the recruitment of type 2 innate lymphoid cells and granulocytes to the upper airways of atopic and healthy subjects following allergen provocation. Soluble mediators in the nasal lining fluid were measured using nasosorption. MEASUREMENTS AND MAIN RESULTS: Following allergen challenge, atopic subjects displayed rapid induction of upper airway symptoms, an enrichment of type 2 innate lymphoid cells, eosinophils and neutrophils, along with increased production of interleukin-5, prostaglandin D2, and eosinophil and T-helper type 2 cell chemokines compared to healthy subjects. The most pronounced type 2 innate lymphoid cell recruitment was observed in patients with elevated serum IgE and airway eosinophilia. CONCLUSIONS: The rapid recruitment of type 2 innate lymphoid cells to the upper airways of allergic rhinitis patients, and their association with key type 2 mediators, highlights their likely important role in the early allergic response to aeroallergen in the airways. The novel methodology described herein enables the analysis of rare cell populations from non-invasive, serial tissue sampling.
Date Issued
2017-01-13
Date Acceptance
2017-01-11
Citation
American Journal of Respiratory and Critical Care Medicine, 2017, 195 (12), pp.1586-1596
URI
http://hdl.handle.net/10044/1/44042
URL
https://www.atsjournals.org/doi/10.1164/rccm.201609-1846OC
DOI
https://www.dx.doi.org/10.1164/rccm.201609-1846OC
ISSN
1535-4970
Publisher
American Thoracic Society
Start Page
1586
End Page
1596
Journal / Book Title
American Journal of Respiratory and Critical Care Medicine
Volume
195
Issue
12
Copyright Statement
© 2017 the American Thoracic Society.
Sponsor
Medical Research Council (MRC)
GlaxoSmithKline Services Unlimited
National Institute for Health Research
Medical Research Council (MRC)
Medical Research Council (MRC)
Asthma UK
Asthma UK
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/28085492
Grant Number
G1100238
n/a
NF-SI-0514-10092
G1000758
G1000758
CH11SJ
CH11SJ
Subjects
Science & Technology
Life Sciences & Biomedicine
Critical Care Medicine
Respiratory System
General & Internal Medicine
ILC2
Th2
allergic airway inflammation
asthma
RECEPTOR-HOMOLOGOUS MOLECULE
CRTH2 ANTAGONIST OC000459
HUMAN EPITHELIAL-CELLS
PROSTAGLANDIN D-2
CONTROLLED ASTHMA
DOUBLE-BLIND
T(H)2 CELLS
BI 671800
IN-VIVO
INFLAMMATION
ILC2
Th2
allergic airway inflammation
asthma
Adolescent
Adult
Allergens
Female
Flow Cytometry
Humans
Immunity, Innate
Lymphocytes
Male
Middle Aged
Nasal Mucosa
Rhinitis, Allergic
Th2 Cells
Young Adult
MRC-GSK Strategic Alliance Consortium
Nasal Mucosa
Lymphocytes
Th2 Cells
Humans
Allergens
Flow Cytometry
Adolescent
Adult
Middle Aged
Female
Male
Immunity, Innate
Young Adult
Rhinitis, Allergic
11 Medical and Health Sciences
Respiratory System
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2017-01-13
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