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

共 50 条

[1] Human Oral Epithelial Cells Suppress T Cell Function via Prostaglandin E2 Secretion
Sanchez-Trincado, Jose L.
Pelaez-Prestel, Hector F.
Lafuente, Esther M.
Reche, Pedro A.
FRONTIERS IN IMMUNOLOGY, 2022, 12
[2] Prostaglandin E2 controls the metabolic adaptation of T cells to the intestinal microenvironment
Villa, Matteo
Sanin, David E.
Apostolova, Petya
Corrado, Mauro
Kabat, Agnieszka M.
Cristinzio, Carmine
Regina, Annamaria
Carrizo, Gustavo E.
Rana, Nisha
Stanczak, Michal A.
Baixauli, Francesc
Grzes, Katarzyna M.
Cupovic, Jovana
Solagna, Francesca
Hackl, Alexandra
Globig, Anna-Maria
Haessler, Fabian
Puleston, Daniel J.
Kelly, Beth
Cabezas-Wallscheid, Nina
Hasselblatt, Peter
Bengsch, Bertram
Zeiser, Robert
Buescher, Joerg M.
Pearce, Edward J.
Pearce, Erika L.
NATURE COMMUNICATIONS, 2024, 15 (01)
[3] The calcium-sensing receptor modulates the prostaglandin E2 pathway in intestinal inflammation
Gushchina, Valeriya
Kupper, Nadja
Schwarzkopf, Michael
Frisch, Gitta
Piatek, Karina
Aigner, Cornelia
Michel, Alexandra
Schueffl, Hemma
Iamartino, Luca
Elajnaf, Taha
Manhardt, Teresa
Vlasaty, Andrea
Heffeter, Petra
Bassetto, Marcella
Kallay, Enikoe
Schepelmann, Martin
FRONTIERS IN PHARMACOLOGY, 2023, 14
[4] Adenosine and prostaglandin E2 production by human inducible regulatory T cells in health and disease
Whiteside, Theresa L.
Jackson, Edwin K.
FRONTIERS IN IMMUNOLOGY, 2013, 4
[5] Prostaglandin E2 Promotes Features of Replicative Senescence in Chronically Activated Human CD8+T Cells
Chou, Jennifer P.
Ramirez, Christina M.
Ryba, Danielle M.
Koduri, Megha P.
Effros, Rita B.
PLOS ONE, 2014, 9 (06):
[6] Adenosine and Prostaglandin E2 Cooperate in the Suppression of Immune Responses Mediated by Adaptive Regulatory T Cells
Mandapathil, Magis
Szczepanski, Miroslaw J.
Szajnik, Marta
Ren, Jin
Jackson, Edwin K.
Johnson, Jonas T.
Gorelik, Elieser
Lang, Stephan
Whiteside, Theresa L.
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (36) : 27571 - 27580
[7] Prostaglandin E2 amplifies IL-17 production by γδ T cells during barrier inflammation
Polese, Barbara
Thurairajah, Bavanitha
Zhang, Hualin
Soo, Cindy Leung
McMahon, Clara A.
Fontes, Ghislaine
Hussain, Sabah N. A.
Abadie, Valerie
King, Irah L.
CELL REPORTS, 2021, 36 (04):
[8] Prostaglandin E2 promotes Pam3CSK4-induced inflammation in endometrial epithelial cells of cattle
Shen, Yuan
Feng, Shuang
Liu, Bo
Ma, Wei
Gao, Ruifeng
Wu, Jindi
Deng, Yang
Gao, Long
Zhang, Shuangyi
Li, Qianru
Cao, Jinshan
ANIMAL REPRODUCTION SCIENCE, 2019, 200 : 51 - 59
[9] Prostaglandin E2 signaling through E prostanoid receptor 2 impairs proliferative response of double negative regulatory T cells
Lee, Boris P. L.
Juvet, Stephen C.
Zhang, Li
INTERNATIONAL IMMUNOPHARMACOLOGY, 2009, 9 (05) : 534 - 539
[10] Dachengqi Decoction alleviates intestinal inflammation in ovalbumin- induced asthma by reducing group 2 innate lymphoid cells in a microbiota-dependent manner
Liu, Zirui
Li, Yalan
Li, Na
Wang, Yongan
Li, Qiuyi
Ge, Dongyu
Peng, Guiying
Zhou, Mengyu
JOURNAL OF TRADITIONAL AND COMPLEMENTARY MEDICINE, 2023, 13 (02): : 183 - 192

← 1 2 3 4 5 →