Microbiotas from Humans with Inflammatory Bowel Disease Alter the Balance of Gut Th17 and RORγt+ Regulatory T Cells and Exacerbate Colitis in Mice

被引：504

作者：

Britton, Graham J. ^{[1
,2
]}

Contijoch, Eduardo J. ^{[1
,2
]}

Mogno, Ilaria ^{[1
,2
]}

Vennaro, Olivia H. ^{[1
,2
]}

Llewellyn, Sean R. ^{[1
,2
]}

Ng, Ruby ^{[1
,2
]}

Li, Zhihua ^{[1
,2
]}

Mortha, Arthur ^{[3
,6
]}

Merad, Miriam ^{[2
,3
]}

Das, Anuk ^{[7
]}

Gevers, Dirk ^{[7
]}

McGovern, Dermot P. B. ^{[8
]}

Singh, Namita ^{[9
]}

Braun, Jonathan ^{[10
]}

Jacobs, Jonathan P. ^{[11
]}

Clemente, Jose C. ^{[1
,2
]}

Grinspan, Ari ^{[4
]}

Sands, Bruce E. ^{[4
]}

Colombel, Jean-Frederic ^{[4
]}

Dubinsky, Marla C. ^{[4
,5
]}

Faith, Jeremiah J. ^{[1
,2
]}

机构：

[1] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Precis Immunol Inst, New York, NY 10029 USA

[3] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA

[4] Icahn Sch Med Mt Sinai, Div Gastroenterol, New York, NY 10029 USA

[5] Icahn Sch Med Mt Sinai, Pediat Gastroenterol & Hepatol, New York, NY 10029 USA

[6] Univ Toronto, Dept Immunol, Toronto, ON, Canada

[7] Janssen Res & Dev LLC, Janssen Human Microbiome Inst, Spring House, PA USA

[8] Cedars Sinai Med Ctr, Inflammatory Bowel & Immunobiol Res Inst, Los Angeles, CA 90048 USA

[9] Cedars Sinai Med Ctr, Pediat Gastroenterol & Inflammatory Bowel Dis, Los Angeles, CA 90048 USA

[10] UCLA, David Geffen Sch Med, Los Angeles, CA 90095 USA

[11] Univ Calif Los Angeles, Dept Med, Div Digest Dis, Los Angeles, CA 90024 USA

来源：

IMMUNITY | 2019年 / 50卷 / 01期

关键词：

ACTIVE ULCERATIVE-COLITIS; INTESTINAL INFLAMMATION; BACTERIA; INDUCTION; COMMENSAL; MODEL; DIFFERENTIATION; TRANSPLANTATION; SUSCEPTIBILITY; IDENTIFICATION;

D O I：

10.1016/j.immuni.2018.12.015

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Microbiota are thought to influence the development and progression of inflammatory bowel disease (IBD), but determining generalizable effects of microbiota on IBD etiology requires larger-scale functional analyses. We colonized germ-free mice with intestinal microbiotas from 30 healthy and IBD donors and determined the homeostatic intestinal T cell response to each microbiota. Compared to microbiotas from healthy donors, transfer of IBD microbiotas into germ-free mice increased numbers of intestinal Th17 cells and Th2 cells and decreased numbers of ROR gamma t(+) Treg cells. Colonization with IBD microbiotas exacerbated disease in a model where colitis is induced upon transfer of naive T cells into Rag1(-/-) mice. The proportions of Th17 and ROR gamma t(+) Treg cells induced by each microbiota were predictive of human disease status and accounted for disease severity in the Rag1(-/-) colitis model. Thus, an impact on intestinal Th17 and ROR gamma t(+) Treg cell compartments emerges as a unifying feature of IBD microbiotas, suggesting a general mechanism for microbial contribution to IBD pathogenesis.

引用

页码：212 / +

页数：17

共 66 条

[1]

Interleukin-23 Drives Intestinal Inflammation through Direct Activity on T Cells [J].

Ahern, Philip P. ;

Schiering, Chris ;

Buonocore, Sofia ;

McGeachy, Mandy J. ;

Cua, Dan J. ;

Maloy, Kevin J. ;

Powrie, Fiona .

IMMUNITY, 2010, 33 (02) :279-288

[2]

Host protective roles of type 2 immunity: Parasite killing and tissue repair, flip sides of the same coin [J].

Allen, Judith E. ;

Sutherland, Tara E. .

SEMINARS IN IMMUNOLOGY, 2014, 26 (04) :329-340

[3]

Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation [J].

Atarashi, Koji ;

Suda, Wataru ;

Luo, Chengwei ;

Kawaguchi, Takaaki ;

Motoo, Iori ;

Narushima, Seiko ;

Kiguchi, Yuya ;

Yasuma, Keiko ;

Watanabe, Eiichiro ;

Tanoue, Takeshi ;

Thaiss, Christoph A. ;

Sato, Mayuko ;

Toyooka, Kiminori ;

Said, Heba S. ;

Yamagami, Hirokazu ;

Rice, Scott A. ;

Gevers, Dirk ;

Johnson, Ryan C. ;

Segre, Julia A. ;

Chen, Kong ;

Kolls, Jay K. ;

Elinav, Eran ;

Morita, Hidetoshi ;

Xavier, Ramnik J. ;

Hattori, Masahira ;

Honda, Kenya .

SCIENCE, 2017, 358 (6361) :359-+

[4]

Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species [J].

Atarashi, Koji ;

Tanoue, Takeshi ;

Shima, Tatsuichiro ;

Imaoka, Akemi ;

Kuwahara, Tomomi ;

Momose, Yoshika ;

Cheng, Genhong ;

Yamasaki, Sho ;

Saito, Takashi ;

Ohba, Yusuke ;

Taniguchi, Tadatsugu ;

Takeda, Kiyoshi ;

Hori, Shohei ;

Ivanov, Ivaylo I. ;

Umesaki, Yoshinori ;

Itoh, Kikuji ;

Honda, Kenya .

SCIENCE, 2011, 331 (6015) :337-341

[5]

Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children [J].

Blanton, Laura V. ;

Charbonneau, Mark R. ;

Salih, Tarek ;

Barratt, Michael J. ;

Venkatesh, Siddarth ;

Ilkaveya, Olga ;

Subramanian, Sathish ;

Manary, Mark J. ;

Trehan, Indi ;

Jorgensen, Josh M. ;

Fan, Yue-mei ;

Henrissat, Bernard ;

Leyn, Semen A. ;

Rodionov, Dmitry A. ;

Osterman, Andrei L. ;

Maleta, KennethM. ;

Newgard, Christopher B. ;

Ashorn, Per ;

Dewey, Kathryn G. ;

Gordon, Jeffrey I. .

SCIENCE, 2016, 351 (6275)

[6]

QIIME allows analysis of high-throughput community sequencing data [J].

Caporaso, J. Gregory ;

Kuczynski, Justin ;

Stombaugh, Jesse ;

Bittinger, Kyle ;

Bushman, Frederic D. ;

Costello, Elizabeth K. ;

Fierer, Noah ;

Pena, Antonio Gonzalez ;

Goodrich, Julia K. ;

Gordon, Jeffrey I. ;

Huttley, Gavin A. ;

Kelley, Scott T. ;

Knights, Dan ;

Koenig, Jeremy E. ;

Ley, Ruth E. ;

Lozupone, Catherine A. ;

McDonald, Daniel ;

Muegge, Brian D. ;

Pirrung, Meg ;

Reeder, Jens ;

Sevinsky, Joel R. ;

Tumbaugh, Peter J. ;

Walters, William A. ;

Widmann, Jeremy ;

Yatsunenko, Tanya ;

Zaneveld, Jesse ;

Knight, Rob .

NATURE METHODS, 2010, 7 (05) :335-336

[7]

Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models [J].

Cekanaviciute, Egle ;

Yoo, Bryan B. ;

Runia, Tessel F. ;

Debelius, Justine W. ;

Singh, Sneha ;

Nelson, Charlotte A. ;

Kanner, Rachel ;

Bencosme, Yadira ;

Lee, Yun Kyung ;

Hauser, Stephen L. ;

Crabtree-Hartman, Elizabeth ;

Sand, Ilana Katz ;

Gacias, Mar ;

Zhu, Yungjiao ;

Casaccia, Patrizia ;

Cree, Bruce A. C. ;

Knight, Rob ;

Mazmanian, Sarkis K. ;

Baranzini, Sergio E. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (40) :10713-10718

[8]

Fecal Lipocalin 2, a Sensitive and Broadly Dynamic Non-Invasive Biomarker for Intestinal Inflammation [J].

Chassaing, Benoit ;

Srinivasan, Gayathri ;

Delgado, Maria A. ;

Young, Andrew N. ;

Gewirtz, Andrew T. ;

Vijay-Kumar, Matam .

PLOS ONE, 2012, 7 (09)

[9]

Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome [J].

Chudnovskiy, Aleksey ;

Mortha, Arthur ;

Kana, Veronika ;

Kennard, Andrea ;

Ramirez, Juan David ;

Rahman, Adeeb ;

Remark, Romain ;

Mogno, Ilaria ;

Ng, Ruby ;

Gnjatic, Sasha ;

Amir, El-ad David ;

Solovyov, Alexander ;

Greenbaum, Benjamin ;

Clemente, Jose ;

Faith, Jeremiah ;

Belkaid, Yasmine ;

Grigg, Michael E. ;

Merad, Miriam .

CELL, 2016, 167 (02) :444-+

[10]

Contijoch E., 2018, bioRxiv, P277095, DOI DOI 10.1101/277095

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