| Literature DB >> 33579710 |
Siobhan Crittenden1, Marie Goepp1, Jolinda Pollock2, Calum T Robb1, Danielle J Smyth3, You Zhou4, Robert Andrews4, Victoria Tyrrell4, Konstantinos Gkikas5, Alexander Adima1, Richard A O'Connor1, Luke Davies4, Xue-Feng Li6, Hatti X Yao1, Gwo-Tzer Ho1, Xiaozhong Zheng1, Amil Mair1, Sonja Vermeren1, Bin-Zhi Qian6, Damian J Mole1, Konstantinos Gerasimidis5, Jürgen K J Schwarze1, Richard M Breyer7, Mark J Arends8, Valerie B O'Donnell4, John P Iredale9, Stephen M Anderton1, Shuh Narumiya10, Rick M Maizels3, Adriano G Rossi1, Sarah E Howie1, Chengcan Yao11.
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.Entities:
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Year: 2021 PMID： 33579710 PMCID： PMC7880593 DOI： 10.1126/sciadv.abd7954
Source DB: PubMed Journal: Sci Adv ISSN： 2375-2548 Impact factor: 14.136