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Prostaglandin E2 promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells

Siobhan Crittenden Orcid Logo, Marie Goepp Orcid Logo, Jolinda Pollock Orcid Logo, Calum T. Robb Orcid Logo, Danielle J. Smyth Orcid Logo, You Zhou Orcid Logo, Robert Andrews Orcid Logo, Victoria Tyrrell Orcid Logo, Konstantinos Gkikas Orcid Logo, Alexander Adima Orcid Logo, Richard A. O’Connor Orcid Logo, Luke Davies Orcid Logo, Xue-Feng Li, Hatti X. Yao, Gwo-Tzer Ho, Xiaozhong Zheng, Amil Mair, Sonja Vermeren Orcid Logo, Bin-Zhi Qian Orcid Logo, Damian J. Mole Orcid Logo, Konstantinos Gerasimidis, Jürgen K. J. Schwarze Orcid Logo, Richard M. Breyer Orcid Logo, Mark J. Arends Orcid Logo, Valerie B. O’Donnell Orcid Logo, John P. Iredale, Stephen M. Anderton, Shuh Narumiya Orcid Logo, Rick M. Maizels, Adriano G. Rossi, Sarah E. Howie Orcid Logo, Chengcan Yao Orcid Logo

Science Advances, Volume: 7, Issue: 7

Swansea University Author: Luke Davies Orcid Logo

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DOI (Published version): 10.1126/sciadv.abd7954

Abstract

The gut microbiota fundamentally regulates intestinal homeostasis and disease partially through mechanisms that involve modulation of regulatory T cells (Tregs), yet how the microbiota-Treg cross-talk is physiologically controlled is incompletely defined. Here, we report that prostaglandin E2 (PGE2)...

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Published in: Science Advances
ISSN: 2375-2548
Published: American Association for the Advancement of Science (AAAS) 2021
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URI: https://cronfa.swan.ac.uk/Record/cronfa61695
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spelling 2022-11-07T14:44:14.7056555 v2 61695 2022-10-31 Prostaglandin E2 promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells ff080296775381560053d5e3a6e81745 0000-0001-7767-4060 Luke Davies Luke Davies true false 2022-10-31 BMS The gut microbiota fundamentally regulates intestinal homeostasis and disease partially through mechanisms that involve modulation of regulatory T cells (Tregs), yet how the microbiota-Treg cross-talk is physiologically controlled is incompletely defined. Here, we report that prostaglandin E2 (PGE2), a well-known mediator of inflammation, inhibits mucosal Tregs in a manner depending on the gut microbiota. PGE2 through its receptor EP4 diminishes Treg-favorable commensal microbiota. Transfer of the gut microbiota that was modified by PGE2-EP4 signaling modulates mucosal Treg responses and exacerbates intestinal inflammation. Mechanistically, PGE2-modified microbiota regulates intestinal mononuclear phagocytes and type I interferon signaling. Depletion of mononuclear phagocytes or deficiency of type I interferon receptor diminishes PGE2-dependent Treg inhibition. Together, our findings provide emergent evidence that PGE2-mediated disruption of microbiota-Treg communication fosters intestinal inflammation. Journal Article Science Advances 7 7 American Association for the Advancement of Science (AAAS) 2375-2548 12 2 2021 2021-02-12 10.1126/sciadv.abd7954 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University Cancer Research UK; MRC UK 2022-11-07T14:44:14.7056555 2022-10-31T12:37:08.3745386 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Siobhan Crittenden 0000-0002-4218-7745 1 Marie Goepp 0000-0003-1659-5689 2 Jolinda Pollock 0000-0002-2260-592x 3 Calum T. Robb 0000-0002-0249-7212 4 Danielle J. Smyth 0000-0001-6080-2679 5 You Zhou 0000-0002-1743-1291 6 Robert Andrews 0000-0002-3491-2361 7 Victoria Tyrrell 0000-0002-2987-118x 8 Konstantinos Gkikas 0000-0003-1581-6566 9 Alexander Adima 0000-0002-6467-4827 10 Richard A. O’Connor 0000-0001-7100-0233 11 Luke Davies 0000-0001-7767-4060 12 Xue-Feng Li 13 Hatti X. Yao 14 Gwo-Tzer Ho 15 Xiaozhong Zheng 16 Amil Mair 17 Sonja Vermeren 0000-0002-8460-0884 18 Bin-Zhi Qian 0000-0002-5796-1078 19 Damian J. Mole 0000-0001-6884-7302 20 Konstantinos Gerasimidis 21 Jürgen K. J. Schwarze 0000-0002-6899-748x 22 Richard M. Breyer 0000-0001-5828-4403 23 Mark J. Arends 0000-0002-6826-8770 24 Valerie B. O’Donnell 0000-0003-4089-8460 25 John P. Iredale 26 Stephen M. Anderton 27 Shuh Narumiya 0000-0001-8062-6529 28 Rick M. Maizels 29 Adriano G. Rossi 30 Sarah E. Howie 0000-0001-7291-3499 31 Chengcan Yao 0000-0003-3754-2842 32 61695__25674__f14adfb329984a828902580df0d947fd.pdf 61695_VoR.pdf 2022-11-07T14:43:08.0009305 Output 10533016 application/pdf Version of Record true Copyright © 2021 The Authors. Distributed under a Creative Commons Attribution License 4.0 (CC BY). true eng https://creativecommons.org/licenses/by/4.0/
title Prostaglandin E2 promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells
spellingShingle Prostaglandin E2 promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells
Luke Davies
title_short Prostaglandin E2 promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells
title_full Prostaglandin E2 promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells
title_fullStr Prostaglandin E2 promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells
title_full_unstemmed Prostaglandin E2 promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells
title_sort Prostaglandin E2 promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells
author_id_str_mv ff080296775381560053d5e3a6e81745
author_id_fullname_str_mv ff080296775381560053d5e3a6e81745_***_Luke Davies
author Luke Davies
author2 Siobhan Crittenden
Marie Goepp
Jolinda Pollock
Calum T. Robb
Danielle J. Smyth
You Zhou
Robert Andrews
Victoria Tyrrell
Konstantinos Gkikas
Alexander Adima
Richard A. O’Connor
Luke Davies
Xue-Feng Li
Hatti X. Yao
Gwo-Tzer Ho
Xiaozhong Zheng
Amil Mair
Sonja Vermeren
Bin-Zhi Qian
Damian J. Mole
Konstantinos Gerasimidis
Jürgen K. J. Schwarze
Richard M. Breyer
Mark J. Arends
Valerie B. O’Donnell
John P. Iredale
Stephen M. Anderton
Shuh Narumiya
Rick M. Maizels
Adriano G. Rossi
Sarah E. Howie
Chengcan Yao
format Journal article
container_title Science Advances
container_volume 7
container_issue 7
publishDate 2021
institution Swansea University
issn 2375-2548
doi_str_mv 10.1126/sciadv.abd7954
publisher American Association for the Advancement of Science (AAAS)
college_str Faculty of Medicine, Health and Life Sciences
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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
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description The gut microbiota fundamentally regulates intestinal homeostasis and disease partially through mechanisms that involve modulation of regulatory T cells (Tregs), yet how the microbiota-Treg cross-talk is physiologically controlled is incompletely defined. Here, we report that prostaglandin E2 (PGE2), a well-known mediator of inflammation, inhibits mucosal Tregs in a manner depending on the gut microbiota. PGE2 through its receptor EP4 diminishes Treg-favorable commensal microbiota. Transfer of the gut microbiota that was modified by PGE2-EP4 signaling modulates mucosal Treg responses and exacerbates intestinal inflammation. Mechanistically, PGE2-modified microbiota regulates intestinal mononuclear phagocytes and type I interferon signaling. Depletion of mononuclear phagocytes or deficiency of type I interferon receptor diminishes PGE2-dependent Treg inhibition. Together, our findings provide emergent evidence that PGE2-mediated disruption of microbiota-Treg communication fosters intestinal inflammation.
published_date 2021-02-12T04:20:42Z
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