The nasal mucosal late allergic reaction to grass pollen involves type 2 inflammation (IL-5 and IL-13), the inflammasome (IL-1β), and complement
File(s)
Accepted version
Supporting information
Author(s)
Type
Journal Article
Abstract
Non-invasive mucosal sampling (nasosorption and nasal curettage) was used following nasal allergen challenge with grass pollen in subjects with allergic rhinitis, in order to define the molecular basis of the late allergic reaction (LAR). It was found that the nasal LAR to grass pollen involves parallel changes in pathways of type 2 inflammation (IL-4, IL-5 and IL-13), inflammasome-related (IL-1β), and complement and circadian-associated genes. A grass pollen nasal spray was given to subjects with hay fever followed by serial sampling, in which cytokines and chemokines were measured in absorbed nasal mucosal lining fluid, and global gene expression (transcriptomics) assessed in nasal mucosal curettage samples. Twelve of 19 subjects responded with elevations in interleukin (IL)-5, IL-13, IL-1β and MIP-1β/CCL4 protein levels in the late phase. In addition, in these individuals whole-genome expression profiling showed upregulation of type 2 inflammation involving eosinophils and IL-4, IL-5 and IL-13; neutrophil recruitment with IL-1α and IL-1β; the alternative pathway of complement (factor P and C5aR); and prominent effects on circadian-associated transcription regulators. Baseline IL-33 mRNA strongly correlated with these late-phase responses, whereas a single oral dose of prednisone dose-dependently reversed most nasal allergen challenge-induced cytokine and transcript responses. This study shows that the LAR to grass pollen involves a range of inflammatory pathways and suggests potential new biomarkers and therapeutic targets. Furthermore, the marked variation in mucosal inflammatory events between different patients suggests that in the future precision mucosal sampling may enable rational specific therapy.
Date Issued
2016-09-28
Date Acceptance
2016-07-21
Citation
Mucosal Immunology, 2016, 10, pp.408-420
ISSN
1935-3456
Publisher
Nature Publishing Group
Start Page
408
End Page
420
Journal / Book Title
Mucosal Immunology
Volume
10
Copyright Statement
© 2016 Society for Mucosal Immunology
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/27677865
PII: mi201674
Grant Number
G1000758
G1000758
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
GENE-EXPRESSION
IMMUNE-RESPONSES
MAST-CELLS
RHINITIS
ASTHMA
AIRWAY
IGE
CHALLENGE
RECEPTOR
DISEASE
Adult
Allergens
Antigens, Plant
Complement System Proteins
Female
Humans
Hypersensitivity
Hypersensitivity, Delayed
Inflammasomes
Interleukin-13
Interleukin-1beta
Interleukin-5
Male
Middle Aged
Nasal Mucosa
Poaceae
Pollen
Prednisone
Th2 Cells
Young Adult
Nasal Mucosa
Th2 Cells
Humans
Poaceae
Pollen
Hypersensitivity
Hypersensitivity, Delayed
Prednisone
Interleukin-5
Interleukin-13
Allergens
Adult
Middle Aged
Complement System Proteins
Female
Male
Antigens, Plant
Interleukin-1beta
Young Adult
Inflammasomes
Immunology
06 Biological Sciences
11 Medical and Health Sciences
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2016-09-28