The central role of IL-33/IL-1RL1 pathway in asthma: From pathogenesis to intervention

A K Saikumar Jayalatha, L Hesse, M E Ketelaar, G H Koppelman, M C Nawijn*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

93 Citations (Scopus)
324 Downloads (Pure)

Abstract

Interleukin-33 (IL-33), a member of the IL-1 family, and its cognate receptor, Interleukin-1 receptor like-1 (IL-1RL1 or ST2), are susceptibility genes for childhood asthma. In response to cellular damage, IL-33 is released from barrier tissues as an & lsquo;alarmin & rsquo; to activate the innate immune response. IL-33 drives type 2 responses by inducing signalling through its receptor IL-1RL1 in several immune and structural cells, thereby leading to type 2 cytokine and chemokine production. IL-1RL1 gene transcript encodes different isoforms generated through alternative splicing. Its soluble isoform, IL-1RL1-a or sST2, acts as a decoy receptor by sequestering IL-33, thereby inhibiting IL1RL1-b/IL-33 signalling. IL-33 and its receptor IL-1RL1 are therefore considered as putative biomarkers or targets for pharmacological intervention in asthma. This review will provide an overview of the genetics and biology of the IL-33/IL-1RL1 pathway in the context of asthma pathogenesis. It will discuss the potential and complexities of targeting the cytokine or its receptor, how genetics or biomarkers may inform precision medicine for asthma targeting this pathway, and the possible positioning of therapeutics targeting IL-33 or its receptor in the expanding landscape of novel biologicals applied in asthma management. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Original languageEnglish
Article number107847
Number of pages18
JournalPharmacology & Therapeutics
Volume225
Early online date2-Apr-2021
DOIs
Publication statusPublished - Sept-2021

Keywords

  • Asthma
  • IL-1RL1
  • IL-33
  • Immune cells
  • Epithelial cells
  • Genetics
  • Pharmacotherapy
  • AIRWAY SMOOTH-MUSCLE
  • INNATE LYMPHOID-CELLS
  • REGULATORY T-CELLS
  • ST2 GENE-PRODUCT
  • MAST-CELLS
  • ATOPIC-DERMATITIS
  • HUMAN BASOPHILS
  • CYTOKINE PRODUCTION
  • DNA METHYLATION
  • PROMOTER USAGE

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