Oxidation of the alarmin IL-33 regulates ST2-dependent inflammation

E. Suzanne Cohen (), Ian C. Scott, Jayesh B. Majithiya, Laura Rapley, Benjamin P. Kemp, Elizabeth England, D. Gareth Rees, Catherine L. Overed-Sayer, Joanne Woods, Nicholas J. Bond, Christel Séguy Veyssier, Kevin J. Embrey, Dorothy A. Sims, Michael R. Snaith, Katherine A. Vousden, Martin D. Strain, Denice T. Y. Chan, Sara Carmen, Catherine E. Huntington, Liz Flavell, Jianqing Xu, Bojana Popovic, Christopher E. Brightling, Tristan J. Vaughan, Robin Butler, David C. Lowe, Daniel R. Higazi, Dominic J. Corkill, Richard D. May, Matthew A. Sleeman and Tomas Mustelin
Additional contact information
E. Suzanne Cohen: Inflammation and Autoimmunity, MedImmune Ltd
Ian C. Scott: Inflammation and Autoimmunity, MedImmune Ltd
Jayesh B. Majithiya: Inflammation and Autoimmunity, MedImmune Ltd
Laura Rapley: Inflammation and Autoimmunity, MedImmune Ltd
Benjamin P. Kemp: MedImmune Ltd
Elizabeth England: MedImmune Ltd
D. Gareth Rees: MedImmune Ltd
Catherine L. Overed-Sayer: Inflammation and Autoimmunity, MedImmune Ltd
Joanne Woods: Inflammation and Autoimmunity, MedImmune Ltd
Nicholas J. Bond: Analytical Biotechnology, MedImmune Ltd
Christel Séguy Veyssier: Analytical Biotechnology, MedImmune Ltd
Kevin J. Embrey: Innovative Medicines, AstraZeneca, Mereside
Dorothy A. Sims: Inflammation and Autoimmunity, MedImmune LLC
Michael R. Snaith: MedImmune Ltd
Katherine A. Vousden: MedImmune Ltd
Martin D. Strain: MedImmune Ltd
Denice T. Y. Chan: MedImmune Ltd
Sara Carmen: MedImmune Ltd
Catherine E. Huntington: MedImmune Ltd
Liz Flavell: Innovative Medicines, AstraZeneca, Mereside
Jianqing Xu: MedImmune Ltd
Bojana Popovic: MedImmune Ltd
Christopher E. Brightling: Immunity and Inflammation, Institute for Lung Health, Leicester LE3 9QP, UK; NIHR Respiratory Biomedical Research Unit, University Hospitals of Leicester
Tristan J. Vaughan: MedImmune Ltd
Robin Butler: MedImmune Ltd
David C. Lowe: MedImmune Ltd
Daniel R. Higazi: Analytical Biotechnology, MedImmune Ltd
Dominic J. Corkill: Inflammation and Autoimmunity, MedImmune Ltd
Richard D. May: Inflammation and Autoimmunity, MedImmune Ltd
Matthew A. Sleeman: Inflammation and Autoimmunity, MedImmune Ltd
Tomas Mustelin: Inflammation and Autoimmunity, MedImmune LLC

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: Abstract In response to infections and irritants, the respiratory epithelium releases the alarmin interleukin (IL)-33 to elicit a rapid immune response. However, little is known about the regulation of IL-33 following its release. Here we report that the biological activity of IL-33 at its receptor ST2 is rapidly terminated in the extracellular environment by the formation of two disulphide bridges, resulting in an extensive conformational change that disrupts the ST2 binding site. Both reduced (active) and disulphide bonded (inactive) forms of IL-33 can be detected in lung lavage samples from mice challenged with Alternaria extract and in sputum from patients with moderate–severe asthma. We propose that this mechanism for the rapid inactivation of secreted IL-33 constitutes a ‘molecular clock’ that limits the range and duration of ST2-dependent immunological responses to airway stimuli. Other IL-1 family members are also susceptible to cysteine oxidation changes that could regulate their activity and systemic exposure through a similar mechanism.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms9327 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9327

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms9327

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().