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

被引：51

作者：

Crittenden, Siobhan ^{[1
]}

Goepp, Marie ^{[1
]}

Pollock, Jolinda ^{[2
]}

Robb, Calum T. ^{[1
]}

Smyth, Danielle J. ^{[3
]}

Zhou, You ^{[4
,5
]}

Andrews, Robert ^{[4
,5
]}

Tyrrell, Victoria ^{[4
,5
]}

Gkikas, Konstantinos ^{[6
]}

Adima, Alexander ^{[1
]}

O'Connor, Richard A. ^{[1
]}

Davies, Luke ^{[4
,5
]}

Li, Xue-Feng ^{[7
]}

Yao, Hatti X. ^{[1
]}

Ho, Gwo-Tzer ^{[1
]}

Zheng, Xiaozhong ^{[1
]}

Mair, Amil ^{[1
]}

Vermeren, Sonja ^{[1
]}

Qian, Bin-Zhi ^{[7
]}

Mole, Damian J. ^{[1
]}

Gerasimidis, Konstantinos ^{[6
]}

Schwarze, Jurgen K. J. ^{[1
]}

Breyer, Richard M. ^{[8
,9
]}

Arends, Mark J. ^{[10
]}

O'Donnell, Valerie B. ^{[4
,5
]}

Iredale, John P. ^{[11
]}

Anderton, Stephen M. ^{[1
]}

Narumiya, Shuh ^{[12
,13
]}

Maizels, Rick M. ^{[3
]}

Rossi, Adriano G. ^{[1
]}

Howie, Sarah E. ^{[1
]}

Yao, Chengcan ^{[1
]}

机构：

[1] Univ Edinburgh, Ctr Inflammat Res, Queens Med Res Inst, Edinburgh EH1 4TJ, Midlothian, Scotland

[2] Scotlands Rural Coll, SRUC Vet Serv, Easter Bush Estate, Aberdeen EH26 0PZ, Scotland

[3] Univ Glasgow, Wellcome Ctr Mol Parasitol, Inst Infect Immun & Inflammat, Glasgow G12 8TA, Lanark, Scotland

[4] Cardiff Univ, Syst Immun Univ Res Inst, Cardiff CF14 4XN, Wales

[5] Cardiff Univ, Div Infect & Immun, Cardiff CF14 4XN, Wales

[6] Univ Glasgow, Sch Med Dent & Nursing, Human Nutr, Glasgow G31 2ER, Lanark, Scotland

[7] Univ Edinburgh, MRC Ctr Reprod Hlth, Queens Med Res Inst, Edinburgh EH16 4TJ, Midlothian, Scotland

[8] Vanderbilt Univ, Med Ctr, Tennessee Valley Hlth Author, Dept Vet Affairs, Nashville, TN USA

[9] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA

[10] Univ Edinburgh, Canc Res UK Edinburgh Ctr, Inst Genet & Mol Med, Div Pathol, Edinburgh EH4 2XR, Midlothian, Scotland

[11] Univ Bristol, Senate House, Bristol BS8 1TH, Avon, England

[12] Kyoto Univ, Med Innovat Ctr, Alliance Lab Adv Med Res, Grad Sch Med, Kyoto 6068507, Japan

[13] Kyoto Univ, Med Innovat Ctr, Dept Drug Discovery Med, Grad Sch Med, Kyoto 6068507, Japan

来源：

SCIENCE ADVANCES | 2021年 / 7卷 / 07期

基金：

欧洲研究理事会; 英国医学研究理事会; 英国惠康基金;

关键词：

CHAIN FATTY-ACIDS; DIFFERENTIATION; HOMEOSTASIS; METABOLITES; BACTERIAL; TH17; ACTIVATION; GENERATION; POPULATION; EXPRESSION;

D O I：

10.1126/sciadv.abd7954

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The gut microbiota fundamentally regulates intestinal homeostasis and disease partially through mechanisms that involve modulation of regulatory T cells (T-regs), yet how the microbiota-T-reg cross-talk is physiologically controlled is incompletely defined. Here, we report that prostaglandin E-2 (PGE(2)), a well-known mediator of inflammation, inhibits mucosal T(regs )in a manner depending on the gut microbiota. PGE(2) through its receptor EP4 diminishes T-reg-favorable commensal microbiota. Transfer of the gut microbiota that was modified by PGE(2)-EP4 signaling modulates mucosal T-reg responses and exacerbates intestinal inflammation. Mechanistically, PGE(2)-modified microbiota regulates intestinal mononuclear phagocytes and type I interferon signaling. Depletion of mononuclear phagocytes or deficiency of type I interferon receptor diminishes PGE(2)-dependent T(reg )inhibition. Together, our findings provide emergent evidence that PGE(2)-mediated disruption of microbiota-T-reg communication fosters intestinal inflammation.

引用

页数：16

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