Th17 Cell Induction by Adhesion of Microbes to Intestinal Epithelial Cells

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2015 Sep 29

PMID 26411289

Citations 535

Authors

Koji Atarashi

Takeshi Tanoue

Minoru Ando

Nobuhiko Kamada

Yuji Nagano

Seiko Narushima

Wataru Suda

Akemi Imaoka

Hiromi Setoyama

Takashi Nagamori

Eiji Ishikawa

Tatsuichiro Shima

Taeko Hara

Shoichi Kado

Toshi Jinnohara

Hiroshi Ohno

Takashi Kondo

Kiminori Toyooka

Eiichiro Watanabe

Shin-Ichiro Yokoyama

Shunji Tokoro

Hiroshi Mori

Yurika Noguchi

Hidetoshi Morita

Ivaylo I Ivanov

Tsuyoshi Sugiyama

Gabriel Nunez

J Gray Camp

Masahira Hattori

Yoshinori Umesaki

Kenya Honda

Affiliations

Soon will be listed here.

Abstract

Intestinal Th17 cells are induced and accumulate in response to colonization with a subgroup of intestinal microbes such as segmented filamentous bacteria (SFB) and certain extracellular pathogens. Here, we show that adhesion of microbes to intestinal epithelial cells (ECs) is a critical cue for Th17 induction. Upon monocolonization of germ-free mice or rats with SFB indigenous to mice (M-SFB) or rats (R-SFB), M-SFB and R-SFB showed host-specific adhesion to small intestinal ECs, accompanied by host-specific induction of Th17 cells. Citrobacter rodentium and Escherichia coli O157 triggered similar Th17 responses, whereas adhesion-defective mutants of these microbes failed to do so. Moreover, a mixture of 20 bacterial strains, which were selected and isolated from fecal samples of a patient with ulcerative colitis on the basis of their ability to cause a robust induction of Th17 cells in the mouse colon, also exhibited EC-adhesive characteristics.

Citing Articles

Bimekizumab in the Treatment of Axial Spondyloarthritis and Psoriatic Arthritis: A New Kid on the Block.

Sarrand J, Baglione L, Bouvy C, Soyfoo M Int J Mol Sci. 2025; 26(5).

PMID: 40076933 PMC: 11899827. DOI: 10.3390/ijms26052315.

Microbiota in inflammatory bowel disease: mechanisms of disease and therapeutic opportunities.

Iliev I, Ananthakrishnan A, Guo C Nat Rev Microbiol. 2025; .

PMID: 40065181 DOI: 10.1038/s41579-025-01163-0.

Rewilding catalyzes maturation of the humoral immune system.

Chen Y, Zaldana K, Yeung F, Vujkovic-Cvijin I, Downie A, Lin J Sci Adv. 2025; 11(10):eads2364.

PMID: 40053586 PMC: 11887799. DOI: 10.1126/sciadv.ads2364.

Unraveling the microbial mysteries: gut microbiota's role in ulcerative colitis.

Ren K, Yong C, Jin Y, Rong S, Xue K, Cao B Front Nutr. 2025; 12:1519974.

PMID: 39996003 PMC: 11847676. DOI: 10.3389/fnut.2025.1519974.

Partially hydrolyzed guar gum attenuates symptoms and modulates the gut microbiota in a model of SARS-CoV-2 infection.

Yang J, Song I, Saito M, Hartanto T, Ichinohe T, Fukuda S Gut Microbiome (Camb). 2025; 6:e1.

PMID: 39944118 PMC: 11810603. DOI: 10.1017/gmb.2024.7.

References

Weaver C, Elson C, Fouser L, Kolls J . The Th17 pathway and inflammatory diseases of the intestines, lungs, and skin. Annu Rev Pathol. 2012; 8:477-512. PMC: 3965671. DOI: 10.1146/annurev-pathol-011110-130318. View

Spits H, Artis D, Colonna M, Diefenbach A, Di Santo J, Eberl G . Innate lymphoid cells--a proposal for uniform nomenclature. Nat Rev Immunol. 2013; 13(2):145-9. DOI: 10.1038/nri3365. View

Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y, Nishikawa H . Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature. 2013; 500(7461):232-6. DOI: 10.1038/nature12331. View

Mortha A, Chudnovskiy A, Hashimoto D, Bogunovic M, Spencer S, Belkaid Y . Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science. 2014; 343(6178):1249288. PMC: 4291125. DOI: 10.1126/science.1249288. View

Stanley A, Thompson K, Hynes A, Brakebusch C, Quondamatteo F . NADPH oxidase complex-derived reactive oxygen species, the actin cytoskeleton, and Rho GTPases in cell migration. Antioxid Redox Signal. 2013; 20(13):2026-42. DOI: 10.1089/ars.2013.5713. View

Goto Y, Panea C, Nakato G, Cebula A, Lee C, Diez M . Segmented filamentous bacteria antigens presented by intestinal dendritic cells drive mucosal Th17 cell differentiation. Immunity. 2014; 40(4):594-607. PMC: 4084624. DOI: 10.1016/j.immuni.2014.03.005. View

Yang Y, Torchinsky M, Gobert M, Xiong H, Xu M, Linehan J . Focused specificity of intestinal TH17 cells towards commensal bacterial antigens. Nature. 2014; 510(7503):152-6. PMC: 4128479. DOI: 10.1038/nature13279. View

Derebe M, Zlatkov C, Gattu S, Ruhn K, Vaishnava S, Diehl G . Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection. Elife. 2014; 3:e03206. PMC: 4129439. DOI: 10.7554/eLife.03206. View

Palm N, de Zoete M, Cullen T, Barry N, Stefanowski J, Hao L . Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell. 2014; 158(5):1000-1010. PMC: 4174347. DOI: 10.1016/j.cell.2014.08.006. View

10.

Camp J, Frank C, Lickwar C, Guturu H, Rube T, Wenger A . Microbiota modulate transcription in the intestinal epithelium without remodeling the accessible chromatin landscape. Genome Res. 2014; 24(9):1504-16. PMC: 4158762. DOI: 10.1101/gr.165845.113. View

11.

Sano T, Huang W, Hall J, Yang Y, Chen A, Gavzy S . An IL-23R/IL-22 Circuit Regulates Epithelial Serum Amyloid A to Promote Local Effector Th17 Responses. Cell. 2015; 163(2):381-93. PMC: 4621768. DOI: 10.1016/j.cell.2015.08.061. View

12.

Nagano K, Taguchi K, Hara T, Yokoyama S, Kawada K, Mori H . Adhesion and colonization of enterohemorrhagic Escherichia coli O157:H7 in cecum of mice. Microbiol Immunol. 2003; 47(2):125-32. DOI: 10.1111/j.1348-0421.2003.tb02795.x. View

13.

Davis C, Savage D . Habitat, succession, attachment, and morphology of segmented, filamentous microbes indigenous to the murine gastrointestinal tract. Infect Immun. 1974; 10(4):948-56. PMC: 423041. DOI: 10.1128/iai.10.4.948-956.1974. View

14.

Klaasen H, Koopman J, Van den Brink M, Bakker M, POELMA F, Beynen A . Intestinal, segmented, filamentous bacteria in a wide range of vertebrate species. Lab Anim. 1993; 27(2):141-50. DOI: 10.1258/002367793780810441. View

15.

Jepson M, Clark M, Simmons N, Hirst B . Actin accumulation at sites of attachment of indigenous apathogenic segmented filamentous bacteria to mouse ileal epithelial cells. Infect Immun. 1993; 61(9):4001-4. PMC: 281108. DOI: 10.1128/iai.61.9.4001-4004.1993. View

16.

Talham G, Jiang H, Bos N, Cebra J . Segmented filamentous bacteria are potent stimuli of a physiologically normal state of the murine gut mucosal immune system. Infect Immun. 1999; 67(4):1992-2000. PMC: 96557. DOI: 10.1128/IAI.67.4.1992-2000.1999. View

17.

Umesaki Y, Setoyama H, Matsumoto S, Imaoka A, Itoh K . Differential roles of segmented filamentous bacteria and clostridia in development of the intestinal immune system. Infect Immun. 1999; 67(7):3504-11. PMC: 116537. DOI: 10.1128/IAI.67.7.3504-3511.1999. View

18.

Mangan P, Harrington L, OQuinn D, Helms W, Bullard D, Elson C . Transforming growth factor-beta induces development of the T(H)17 lineage. Nature. 2006; 441(7090):231-4. DOI: 10.1038/nature04754. View

19.

Johansson M, Phillipson M, Petersson J, Velcich A, Holm L, Hansson G . The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci U S A. 2008; 105(39):15064-9. PMC: 2567493. DOI: 10.1073/pnas.0803124105. View

20.

Atarashi K, Nishimura J, Shima T, Umesaki Y, Yamamoto M, Onoue M . ATP drives lamina propria T(H)17 cell differentiation. Nature. 2008; 455(7214):808-12. DOI: 10.1038/nature07240. View