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Tissue‐resident macrophages actively suppress IL‐1beta release via a reactive prostanoid/IL‐10 pathway

Natacha Ipseiz, Robert J Pickering Orcid Logo, Marcela Rosas, Victoria J Tyrrell, Luke Davies Orcid Logo, Selinda J Orr, Magdalena A Czubala, Dina Fathalla, Avril AB Robertson, Clare E Bryant Orcid Logo, Valerie O'Donnell, Philip R Taylor Orcid Logo

The EMBO Journal, Volume: 39, Issue: 14

Swansea University Author: Luke Davies Orcid Logo

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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...

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Published in: The EMBO Journal
ISSN: 0261-4189 1460-2075
Published: EMBO 2020
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URI: https://cronfa.swan.ac.uk/Record/cronfa61683
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spelling 2022-11-07T15:36:59.3061183 v2 61683 2022-10-31 Tissue‐resident macrophages actively suppress IL‐1beta release via a reactive prostanoid/IL‐10 pathway ff080296775381560053d5e3a6e81745 0000-0001-7767-4060 Luke Davies Luke Davies true false 2022-10-31 BMS 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. Journal Article The EMBO Journal 39 14 EMBO 0261-4189 1460-2075 s IL-10; IL-1beta; macrophages; prostacyclin 2 6 2020 2020-06-02 10.15252/embj.2019103454 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 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 2022-11-07T15:36:59.3061183 2022-10-31T12:00:48.9722966 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Natacha Ipseiz 1 Robert J Pickering 0000-0003-3332-9868 2 Marcela Rosas 3 Victoria J Tyrrell 4 Luke Davies 0000-0001-7767-4060 5 Selinda J Orr 6 Magdalena A Czubala 7 Dina Fathalla 8 Avril AB Robertson 9 Clare E Bryant 0000-0002-2924-0038 10 Valerie O'Donnell 11 Philip R Taylor 0000-0003-0163-1421 12 61683__25681__6f879dc7e1fc4e32aa8a3e694bd6c841.pdf 61683.pdf 2022-11-07T15:34:47.2168878 Output 1257668 application/pdf Version of Record true Copyright: 2020 The Authors. Published under the terms of the CC BY 4.0 license true eng http://creativecommons.org/licenses/by/4.0/
title Tissue‐resident macrophages actively suppress IL‐1beta release via a reactive prostanoid/IL‐10 pathway
spellingShingle Tissue‐resident macrophages actively suppress IL‐1beta release via a reactive prostanoid/IL‐10 pathway
Luke Davies
title_short Tissue‐resident macrophages actively suppress IL‐1beta release via a reactive prostanoid/IL‐10 pathway
title_full Tissue‐resident macrophages actively suppress IL‐1beta release via a reactive prostanoid/IL‐10 pathway
title_fullStr Tissue‐resident macrophages actively suppress IL‐1beta release via a reactive prostanoid/IL‐10 pathway
title_full_unstemmed Tissue‐resident macrophages actively suppress IL‐1beta release via a reactive prostanoid/IL‐10 pathway
title_sort Tissue‐resident macrophages actively suppress IL‐1beta release via a reactive prostanoid/IL‐10 pathway
author_id_str_mv ff080296775381560053d5e3a6e81745
author_id_fullname_str_mv ff080296775381560053d5e3a6e81745_***_Luke Davies
author Luke Davies
author2 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
format Journal article
container_title The EMBO Journal
container_volume 39
container_issue 14
publishDate 2020
institution Swansea University
issn 0261-4189
1460-2075
doi_str_mv 10.15252/embj.2019103454
publisher EMBO
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description 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.
published_date 2020-06-02T04:20:41Z
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score 11.037581

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