Allergy - 2022 - Badi - IL1RAP expression and the enrichment of IL‐33 activation signatures in severe neutrophilic asthma.pdf (5.9 MB)
Download file

IL1RAP expression and the enrichment of IL-33 activation signatures in severe neutrophilic asthma.

Download (5.9 MB)
journal contribution
posted on 16.09.2022, 10:17 authored by Yusef Eamon Badi, Barbora Salcman, Adam Taylor, Batika Rana, Nazanin Zounemat Kermani, John H Riley, Sally Worsley, Sharon Mumby, Sven-Eric Dahlen, David Cousins, Silvia Bulfone-Paus, Karen Affleck, Kian Fan Chung, Stewart Bates, Ian M Adcock


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.


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.


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.


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.


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.


Biotechnology and Biological Sciences Research Council. Grant Number: BIDS3000032503

Imperial College Jameel Trust

MRC-GSK Alliance: Mechanisms of interplay between allergy and viruses in asthma

Medical Research Council

Find out more...

National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) Leicester

United Kingdom Refractory Asthma Stratification Programme (RASP-UK)

Medical Research Council

Find out more...

MICA: Korea-UK PRISM consortium: Establishing Precision Medicine in severe asthma

Medical Research Council

Find out more...

MRC-Asthma UK Centre in Allergic Mechanisms of Asthma

Medical Research Council

Find out more...

National Institute for Health Research (NIHR) BRC at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London

Asthma UK. Grant Number: 09/020

Imperial College London

Flow cytometric isolation and characterisation of cells from human lung samples

Wellcome Trust

Find out more...

Health assessment across biological length scales for personal pollution exposure and its mitigation (INHALE)

Engineering and Physical Sciences Research Council

Find out more...

'COVAIR': Is SARS-CoV-2 airborne and does it interact with particle pollutants?

Engineering and Physical Sciences Research Council

Find out more...

Innovative Medicines Initiative (IMI). Grant Numbers: No.831434, No.853850, No.115010


Author affiliation

Department of Respiratory Sciences, University of Leicester


VoR (Version of Record)

Published in








Copyright date


Available date


Spatial coverage




Usage metrics