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


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.

SUBMITTER: Crittenden S 

PROVIDER: S-EPMC7880593 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Prostaglandin E<sub>2</sub> promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells.

Crittenden Siobhan S   Goepp Marie M   Pollock Jolinda J   Robb Calum T CT   Smyth Danielle J DJ   Zhou You Y   Andrews Robert R   Tyrrell Victoria V   Gkikas Konstantinos K   Adima Alexander A   O'Connor Richard A RA   Davies Luke L   Li Xue-Feng XF   Yao Hatti X HX   Ho Gwo-Tzer GT   Zheng Xiaozhong X   Mair Amil A   Vermeren Sonja S   Qian Bin-Zhi BZ   Mole Damian J DJ   Gerasimidis Konstantinos K   Schwarze Jürgen K J JKJ   Breyer Richard M RM   Arends Mark J MJ   O'Donnell Valerie B VB   Iredale John P JP   Anderton Stephen M SM   Narumiya Shuh S   Maizels Rick M RM   Rossi Adriano G AG   Howie Sarah E SE   Yao Chengcan C  

Science advances 20210212 7


The gut microbiota fundamentally regulates intestinal homeostasis and disease partially through mechanisms that involve modulation of regulatory T cells (T<sub>regs</sub>), yet how the microbiota-T<sub>reg</sub> cross-talk is physiologically controlled is incompletely defined. Here, we report that prostaglandin E<sub>2</sub> (PGE<sub>2</sub>), a well-known mediator of inflammation, inhibits mucosal T<sub>regs</sub> in a manner depending on the gut microbiota. PGE<sub>2</sub> through its receptor  ...[more]

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