Search: onr:"swepub:oai:lup.lub.lu.se:80c1670a-3f47-449a-a218-a5eed00ac8af" >
Oxidised IL-33 driv...
-
Strickson, SamAstraZeneca, UK
(author)
Oxidised IL-33 drives COPD epithelial pathogenesis via ST2-independent RAGE/EGFR signalling complex
- Article/chapterEnglish2023
Publisher, publication year, extent ...
Numbers
-
LIBRIS-ID:oai:lup.lub.lu.se:80c1670a-3f47-449a-a218-a5eed00ac8af
-
https://lup.lub.lu.se/record/80c1670a-3f47-449a-a218-a5eed00ac8afURI
-
https://doi.org/10.1183/13993003.02210-2022DOI
Supplementary language notes
-
Language:English
-
Summary in:English
Part of subdatabase
Classification
-
Subject category:art swepub-publicationtype
-
Subject category:ref swepub-contenttype
Notes
-
Background Epithelial damage, repair and remodelling are critical features of chronic airway diseases including chronic obstructive pulmonary disease (COPD). Interleukin (IL)-33 released from damaged airway epithelia causes inflammation via its receptor, serum stimulation-2 (ST2). Oxidation of IL-33 to a non-ST2-binding form (IL-33ox) is thought to limit its activity. We investigated whether IL-33ox has functional activities that are independent of ST2 in the airway epithelium. Methods In vitro epithelial damage assays and three-dimensional, air–liquid interface (ALI) cell culture models of healthy and COPD epithelia were used to elucidate the functional role of IL-33ox. Transcriptomic changes occurring in healthy ALI cultures treated with IL-33ox and COPD ALI cultures treated with an IL-33-neutralising antibody were assessed with bulk and single-cell RNA sequencing analysis. Results We demonstrate that IL-33ox forms a complex with receptor for advanced glycation end products (RAGE) and epidermal growth factor receptor (EGFR) expressed on airway epithelium. Activation of this alternative, ST2-independent pathway impaired epithelial wound closure and induced airway epithelial remodelling in vitro. IL-33ox increased the proportion of mucus-producing cells and reduced epithelial defence functions, mimicking pathogenic traits of COPD. Neutralisation of the IL-33ox pathway reversed these deleterious traits in COPD epithelia. Gene signatures defining the pathogenic effects of IL-33ox were enriched in airway epithelia from patients with severe COPD. Conclusions Our study reveals for the first time that IL-33, RAGE and EGFR act together in an ST2-independent pathway in the airway epithelium and govern abnormal epithelial remodelling and mucoobstructive features in COPD.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
-
Houslay, Kirsty F.AstraZeneca, UK
(author)
-
Negri, Victor A.AstraZeneca, UK
(author)
-
Ohne, YoichiroAstraZeneca, UK
(author)
-
Ottosson, TomasAstraZeneca, Sweden
(author)
-
Dodd, Roger B.AstraZeneca, UK
(author)
-
Huntington, Catherine ChaillanAstraZeneca, UK
(author)
-
Baker, TinaAstraZeneca, UK
(author)
-
Li, JingjingAstraZeneca, UK
(author)
-
Stephenson, Katherine E.AstraZeneca, UK
(author)
-
O’Connor, Andy J.AstraZeneca, UK
(author)
-
Sagawe, J. SophieAstraZeneca, UK
(author)
-
Killick, HelenAstraZeneca, UK
(author)
-
Moore, TomAstraZeneca, UK
(author)
-
Rees, D. GarethAstraZeneca, UK
(author)
-
Koch, SofiaAstraZeneca, UK
(author)
-
Sanden, CarolineLund University,Lunds universitet,Luftvägsinflammation,Forskargrupper vid Lunds universitet,Airway Inflammation and Immunology,Lund University Research Groups,Medetect AB(Swepub:lu)mphy-cgu
(author)
-
Wang, YixinAstraZeneca, Sweden
(author)
-
Gubbins, EliseAstraZeneca, UK
(author)
-
Ghaedi, MahboobeAstraZeneca, UK
(author)
-
Kolbeck, RolandAstraZeneca, UK
(author)
-
Saumyaa, SaumyaaAstraZeneca, Sweden
(author)
-
Erjefält, Jonas S.Lund University,Lunds universitet,Luftvägsinflammation,Forskargrupper vid Lunds universitet,DCD transplantation av lungor,Airway Inflammation and Immunology,Lund University Research Groups,DCD transplantation of lungs,Skåne University Hospital(Swepub:lu)mphy-jer
(author)
-
Sims, Gary P.AstraZeneca, UK
(author)
-
Humbles, Alison A.AstraZeneca, UK
(author)
-
Scott, Ian C.AstraZeneca, UK
(author)
-
Ros, Xavier RomeroAstraZeneca, UK
(author)
-
Cohen, E. SuzanneAstraZeneca, UK
(author)
-
AstraZeneca, UKAstraZeneca, Sweden
(creator_code:org_t)
Related titles
-
In:European Respiratory Journal62:30903-1936
Internet link
Find in a library
To the university's database
- By the author/editor
-
Strickson, Sam
-
Houslay, Kirsty ...
-
Negri, Victor A.
-
Ohne, Yoichiro
-
Ottosson, Tomas
-
Dodd, Roger B.
-
show more...
-
Huntington, Cath ...
-
Baker, Tina
-
Li, Jingjing
-
Stephenson, Kath ...
-
O’Connor, Andy J ...
-
Sagawe, J. Sophi ...
-
Killick, Helen
-
Moore, Tom
-
Rees, D. Gareth
-
Koch, Sofia
-
Sanden, Caroline
-
Wang, Yixin
-
Gubbins, Elise
-
Ghaedi, Mahboobe
-
Kolbeck, Roland
-
Saumyaa, Saumyaa
-
Erjefält, Jonas ...
-
Sims, Gary P.
-
Humbles, Alison ...
-
Scott, Ian C.
-
Ros, Xavier Rome ...
-
Cohen, E. Suzann ...
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Respiratory Medi ...
- Articles in the publication
-
European Respira ...
- By the university
-
Lund University