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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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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), 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.
College: Faculty of Medicine, Health and Life Sciences
Funders: Cancer Research UK; MRC UK
Issue: 7