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

Siobhan Crittenden, Marie Goepp, Jolinda Pollock, Calum 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 MoleKonstantinos Gerasimidis, Jürgen 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 M Howie, Chengcan Yao

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 crosstalk 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. Taken together, our findings provide emergent evidence that PGE2-mediated disruption of microbiota-Treg communication fosters intestinal inflammation
Original languageEnglish
JournalScience Advances
Publication statusPublished - 12 Feb 2021


Dive into the research topics of 'Prostaglandin E2 promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells'. Together they form a unique fingerprint.

Cite this