Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Sep:225:107847.
doi: 10.1016/j.pharmthera.2021.107847. Epub 2021 Apr 2.

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

A K Saikumar Jayalatha  1 , L Hesse  1 , M E Ketelaar  2 , G H Koppelman  3 , M C Nawijn  4
Affiliations
Free article
Review

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

A K Saikumar Jayalatha et al. Pharmacol Ther. 2021 Sep.
Free article

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 'alarmin' 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.

Keywords: Asthma; Epithelial cells; Genetics; IL-1RL1; IL-33; Immune cells; Pharmacotherapy.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest MCN reports that his research is supported by grants from GlaxoSmithKline Pharmaceuticals Ltd (GSK). GHK reports grants from GSK and Lung Foundation Netherlands during the conduct of the study, grants from Lung Foundation Netherlands, TEVA Netherlands, Ubbo Emmius Foundation, TETRI Voundation, Vertexand European Union (H2020 program) outside the submitted work and that he has participated in advisory boards to GSK and PURE-IMS (money to institution). AKSJ, LH and MK have nothing to disclose.

Substances