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Prostaglandin E2 promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells
,
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
Science Advances, Volume: 7, Issue: 7
Swansea University Author:
Luke Davies
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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)...
| Published in: | Science Advances |
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| ISSN: | 2375-2548 |
| Published: |
American Association for the Advancement of Science (AAAS)
2021
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa61695 |
| 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. |
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| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
Cancer Research UK; MRC UK |
| Issue: |
7 |