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Tissue‐resident macrophages actively suppress IL‐1beta release via a reactive prostanoid/IL‐10 pathway
Natacha Ipseiz,
Robert J Pickering 
,
Marcela Rosas,
Victoria J Tyrrell,
Luke Davies ,
Selinda J Orr,
Magdalena A Czubala,
Dina Fathalla,
Avril AB Robertson,
Clare E Bryant ,
Valerie O'Donnell,
Philip R Taylor
,
Marcela Rosas,
Victoria J Tyrrell,
Luke Davies ,
Selinda J Orr,
Magdalena A Czubala,
Dina Fathalla,
Avril AB Robertson,
Clare E Bryant ,
Valerie O'Donnell,
Philip R Taylor
The EMBO Journal, Volume: 39, Issue: 14
Swansea University Author:
Luke Davies
-
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Copyright: 2020 The Authors. Published under the terms of the CC BY 4.0 license
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DOI (Published version): 10.15252/embj.2019103454
Abstract
The alarm cytokine interleukin-1β (IL-1β) is a potent activator of the inflammatory cascade following pathogen recognition. IL-1β production typically requires two signals: first, priming by recognition of pathogen-associated molecular patterns leads to the production of immature pro-IL-1β; subseque...
| Published in: | The EMBO Journal |
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| ISSN: | 0261-4189 1460-2075 |
| Published: |
EMBO
2020
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa61683 |
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| Abstract: |
The alarm cytokine interleukin-1β (IL-1β) is a potent activator of the inflammatory cascade following pathogen recognition. IL-1β production typically requires two signals: first, priming by recognition of pathogen-associated molecular patterns leads to the production of immature pro-IL-1β; subsequently, inflammasome activation by a secondary signal allows cleavage and maturation of IL-1β from its pro-form. However, despite the important role of IL-1β in controlling local and systemic inflammation, its overall regulation is still not fully understood. Here we demonstrate that peritoneal tissue-resident macrophages use an active inhibitory pathway, to suppress IL-1β processing, which can otherwise occur in the absence of a second signal. Programming by the transcription factor Gata6 controls the expression of prostacyclin synthase, which is required for prostacyclin production after lipopolysaccharide stimulation and optimal induction of IL-10. In the absence of secondary signal, IL-10 potently inhibits IL-1β processing, providing a previously unrecognized control of IL-1β in tissue-resident macrophages. |
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| Keywords: |
s IL-10; IL-1beta; macrophages; prostacyclin |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
Wellcome Trust (WT). Grant Numbers: 107964/Z/15/Z, 103973/Z/14/Z, 108045/Z/15/Z;
Wellcome Trust and the Royal Society. Grant Number: 099953/Z/12/Z;
UK Research and Innovation|Medical Research Council (MRC). Grant Number: Dementia Research Institute |
| Issue: |
14 |