Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/37066
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dc.contributor.authorCohen, E. S.-
dc.contributor.authorScott, I. C.-
dc.contributor.authorMajithiya, J. B.-
dc.contributor.authorRapley, L.-
dc.contributor.authorKemp, B. P.-
dc.contributor.authorEngland, E.-
dc.contributor.authorRees, D. G.-
dc.contributor.authorOvered-Sayer, C. L.-
dc.contributor.authorWoods, J.-
dc.contributor.authorBond, N. J.-
dc.contributor.authorVeyssier, C. S.-
dc.contributor.authorEmbrey, K. J.-
dc.contributor.authorSims, D. A.-
dc.contributor.authorSnaith, M. R.-
dc.contributor.authorVousden, K. A.-
dc.contributor.authorStrain, M. D.-
dc.contributor.authorChan, D. T.-
dc.contributor.authorCarmen, S.-
dc.contributor.authorHuntington, C. E.-
dc.contributor.authorFlavell, L.-
dc.contributor.authorXu, J.-
dc.contributor.authorPopovic, B.-
dc.contributor.authorBrightling, Christopher Edward-
dc.contributor.authorVaughan, T. J.-
dc.contributor.authorButler, R.-
dc.contributor.authorLowe, D. C.-
dc.contributor.authorHigazi, D. R.-
dc.contributor.authorCorkill, D. J.-
dc.contributor.authorMay, R. D.-
dc.contributor.authorSleeman, M. A.-
dc.contributor.authorMustelin, T.-
dc.date.accessioned2016-03-16T09:59:58Z-
dc.date.available2016-03-16T09:59:58Z-
dc.date.issued2015-09-14-
dc.identifier.citationNature Communications, 2015, 6 : 8327en
dc.identifier.urihttp://www.nature.com/ncomms/2015/150914/ncomms9327/full/ncomms9327.htmlen
dc.identifier.urihttp://hdl.handle.net/2381/37066-
dc.description.abstractIn 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.en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.urihttp://www.ncbi.nlm.nih.gov/pubmed/26365875-
dc.rightsCopyright © 2015, Macmillan Publishers Limited. All rights reserved. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/en
dc.subjectBiological sciencesen
dc.subjectBiochemistryen
dc.subjectImmunologyen
dc.titleOxidation of the alarmin IL-33 regulates ST2-dependent inflammationen
dc.typeJournal Articleen
dc.identifier.doi10.1038/ncomms9327-
dc.identifier.eissn2041-1723-
dc.identifier.piincomms9327-
dc.description.statusPeer-revieweden
dc.description.versionPublisher Versionen
dc.type.subtypeJournal Article;Research Support, Non-U.S. Gov't-
pubs.organisational-group/Organisationen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGYen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicineen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammationen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themesen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themes/Molecular & Cellular Bioscienceen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themes/Respiratory Scienceen
dc.dateaccepted2015-08-11-
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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