RT Journal Article
SR Electronic
T1 Late Breaking Abstract - Enhanced IL-33 response in differentiated human TH2 cells carrying the IL-1RL1 asthma risk genotype
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA2530
DO 10.1183/13993003.congress-2021.PA2530
VO 58
IS suppl 65
A1 Akshaya Keerthi Saikumar Jayalatha
A1 Laura Hesse
A1 Marlies Ketelaar
A1 Maarten Van Den Berge
A1 Victor Gurvey
A1 Gerard Koppelman
A1 Martijn Nawijn
YR 2021
UL http://erj.ersjournals.com/content/58/suppl_65/PA2530.abstract
AB Rationale: IL-33 and its receptor IL-1RL1 are important asthma genes. T helper-2 (TH2) cells present in asthmatic airway wall contribute to chronic inflammation and epithelial remodeling. TH2 cells express IL-1RL1 and respond to IL-33 by increased cytokine production upon stimulation. We aimed to test the extent of the IL-33-driven modification of TH2 cell activation based on asthma-susceptibility alleles of IL-1RL1 gene.Methods: Results: Presence of IL-33 during CD3/CD28 stimulation of TH2 effector cells in-vitro results in extensive changes in gene expression, affecting up to 40% of the transcriptomic changes induced by TH2 cell activation. Nearly, 5-fold change in gene expression was induced by IL-33 in TH2 cells carrying the IL-1RL1 risk haplotype compared to the protective haplotype. In addition, significant differences in IL-33 regulated genes were observed between TH2 cells derived from healthy controls and asthma patients.Conclusions: The asthma-associated IL-1RL1 haplotype strongly increased the sensitivity of TH2 effector cell for IL-33-mediated regulation of gene expression, while disease status also has an independent effect. IL-33 in the airway wall will contribute to chronic inflammation maintained by TH2 effector cells mainly in patients with asthma carrying the IL-1RL1 asthma risk alleles.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA2530.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).