Imperial College London
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ProfessorIanAdcock

Faculty of Medicine, National Heart & Lung Institute

Professor of Respiratory Cell & Molecular Biology
 
 
 
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Contact

 

+44 (0)20 7594 7840ian.adcock Website

 
 
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Location

 

304Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Adcock:2022:10.1111/all.15487,
author = {Adcock, I and Badi, Y and salcman, B and Taylor, A and Rana, B and Zounemat, Kermani N and Riley, JH and Worsley, S and Mumby, S and Dahlen, S-E and Cousins, D and Bulfone-Paus, S and Affleck, K and Chung, KF and Bates, S},
doi = {10.1111/all.15487},
journal = {Allergy},
pages = {156--167},
title = {IL1RAP expression and the enrichment of IL-33 activation signatures in severe neutrophilic asthma},
url = {http://dx.doi.org/10.1111/all.15487},
volume = {78},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background:Interleukin (IL)-33 is an upstream regulator of type 2 (T2) eosinophilic inflammation and has been proposed as a key driver of some asthma phenotypes.Objective:To derive gene signatures from in vitro studies of IL-33-stimulated cells and use these to determine IL-33-associated enrichment patterns in asthma.Methods:Signatures downstream of IL-33 stimulation were derived from our in vitro study of human mast cells and from public datasets of in vitro stimulated human basophils, type 2 innate lymphoid cells (ILC2), regulatory T cells (Treg) and endothelial cells. Gene Set Variation Analysis (GSVA) was used to probe U-BIOPRED and ADEPT sputum transcriptomics to determine enrichment scores (ES) for each signature according to asthma severity, sputum granulocyte status and previously defined molecular phenotypes.Results:IL-33-activated gene signatures were cell-specific with little gene overlap. Individual signatures, however, were associated with similar signalling pathways (TNF, NF-κB, IL-17 and JAK/STAT signalling) and immune cell differentiation pathways (Th17, Th1 and Th2 differentiation). ES for IL-33-activated gene signatures were significantly enriched in asthmatic sputum, particularly in patients with neutrophilic and mixed granulocytic phenotypes. IL-33 mRNA expression was not elevated in asthma whereas the expression of mRNA for IL1RL1, the IL-33 receptor, was up-regulated in the sputum of severe eosinophilic asthma. The mRNA expression for IL1RAP, the IL1RL1 co-receptor, was greatest in severe neutrophilic and mixed granulocytic asthma.Conclusions:IL-33-activated gene signatures are elevated in neutrophilic and mixed granulocytic asthma corresponding with IL1RAP co-receptor expression. This suggests incorporating T2-low asthma in anti-IL-33 trials.
AU  - Adcock,I
AU  - Badi,Y
AU  - salcman,B
AU  - Taylor,A
AU  - Rana,B
AU  - Zounemat,Kermani N
AU  - Riley,JH
AU  - Worsley,S
AU  - Mumby,S
AU  - Dahlen,S-E
AU  - Cousins,D
AU  - Bulfone-Paus,S
AU  - Affleck,K
AU  - Chung,KF
AU  - Bates,S
DO  - 10.1111/all.15487
EP  - 167
PY  - 2022///
SN  - 0105-4538
SP  - 156
TI  - IL1RAP expression and the enrichment of IL-33 activation signatures in severe neutrophilic asthma
T2  - Allergy
UR  - http://dx.doi.org/10.1111/all.15487
UR  - http://hdl.handle.net/10044/1/107275
VL  - 78
ER  -
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