PT  - JOURNAL ARTICLE
AU  - Siobhan Crittenden
AU  - Marie Goepp
AU  - Jolinda Pollock
AU  - Calum T. Robb
AU  - Danielle J. Smyth
AU  - You Zhou
AU  - Robert Andrews
AU  - Victoria Tyrrell
AU  - Alexander Adima
AU  - Richard A. O’Connor
AU  - Luke Davies
AU  - Xue-Feng Li
AU  - Hatti X. Yao
AU  - Gwo-Tzer Ho
AU  - Xiaozhong Zheng
AU  - Amil Mair
AU  - Sonja Vermeren
AU  - Bin-Zhi Qian
AU  - Damian J. Mole
AU  - Jürgen K.J. Schwarze
AU  - Richard M. Breyer
AU  - Mark J. Arends
AU  - Valerie B. O’Donnell
AU  - John P. Iredale
AU  - Stephen M. Anderton
AU  - Shuh Narumiya
AU  - Rick M. Maizels
AU  - Adriano G. Rossi
AU  - Sarah E. Howie
AU  - Chengcan Yao
TI  - Prostaglandin E<sub>2</sub> promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells
AID  - 10.1101/2020.07.12.199513
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.12.199513
4099  - http://biorxiv.org/content/early/2020/07/12/2020.07.12.199513.short
4100  - http://biorxiv.org/content/early/2020/07/12/2020.07.12.199513.full
AB  - 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 contracts PGE2-dependent Treg inhibition. Taken together, our findings provide emergent evidence that PGE2-mediated disruption of microbiota-Treg communication fosters intestinal inflammation.Competing Interest StatementThe authors have declared no competing interest.