Innate lymphoid cells regulate intestinal epithelial cell glycosylation

Yoshiyuki Goto; Takashi Obata; Jun Kunisawa; Shintaro Sato; Ivaylo I Ivanov; Aayam Lamichhane; Natsumi Takeyama; Mariko Kamioka; Mitsuo Sakamoto; Takahiro Matsuki; Hiromi Setoyama; Akemi Imaoka; Satoshi Uematsu; Shizuo Akira; Steven E Domino; Paulina Kulig; Burkhard Becher; Jean-Christophe Renauld; Chihiro Sasakawa; Yoshinori Umesaki; Yoshimi Benno; Hiroshi Kiyono

doi:10.1126/science.1254009

Innate lymphoid cells regulate intestinal epithelial cell glycosylation

Science. 2014 Sep 12;345(6202):1254009. doi: 10.1126/science.1254009. Epub 2014 Aug 21.

Authors

Yoshiyuki Goto¹, Takashi Obata², Jun Kunisawa³, Shintaro Sato⁴, Ivaylo I Ivanov⁵, Aayam Lamichhane⁶, Natsumi Takeyama⁷, Mariko Kamioka⁶, Mitsuo Sakamoto⁸, Takahiro Matsuki⁹, Hiromi Setoyama⁹, Akemi Imaoka⁹, Satoshi Uematsu¹⁰, Shizuo Akira¹¹, Steven E Domino¹², Paulina Kulig¹³, Burkhard Becher¹³, Jean-Christophe Renauld¹⁴, Chihiro Sasakawa¹⁵, Yoshinori Umesaki⁹, Yoshimi Benno¹⁶, Hiroshi Kiyono¹⁷

Affiliations

¹ Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan. Microbe Division/Japan Collection of Microorganisms, RIKEN BioResource Center, Tsukuba 305-0074, Japan.
² Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Microbe Division/Japan Collection of Microorganisms, RIKEN BioResource Center, Tsukuba 305-0074, Japan.
³ Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Osaka 567-0085, Japan. Division of Mucosal Immunology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
⁴ Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
⁵ Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
⁶ Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
⁷ Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Nippon Institute for Biological Science, Tokyo 198-0024, Japan.
⁸ Microbe Division/Japan Collection of Microorganisms, RIKEN BioResource Center, Tsukuba 305-0074, Japan.
⁹ Yakult Central Institute, Tokyo 186-8650, Japan.
¹⁰ Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Department of Mucosal Immunology, School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba, 260-8670, Japan.
¹¹ Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
¹² Department of Obstetrics and Gynecology, Cellular and Molecular Biology Program, University of Michigan Medical Center, Ann Arbor, MI 48109-5617, USA.
¹³ Institute of Experimental Immunology, University of Zürich, Winterthurerstrasse 190, Zürich CH-8057, Switzerland.
¹⁴ Ludwig Institute for Cancer Research and Université Catholique de Louvain, Brussels B-1200, Belgium.
¹⁵ Nippon Institute for Biological Science, Tokyo 198-0024, Japan. Division of Bacterial Infection, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan.
¹⁶ Benno Laboratory, Innovation Center, RIKEN, Wako, Saitama 351-0198, Japan.
¹⁷ Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan. Division of Mucosal Immunology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.

Abstract

Fucosylation of intestinal epithelial cells, catalyzed by fucosyltransferase 2 (Fut2), is a major glycosylation mechanism of host-microbiota symbiosis. Commensal bacteria induce epithelial fucosylation, and epithelial fucose is used as a dietary carbohydrate by many of these bacteria. However, the molecular and cellular mechanisms that regulate the induction of epithelial fucosylation are unknown. Here, we show that type 3 innate lymphoid cells (ILC3) induced intestinal epithelial Fut2 expression and fucosylation in mice. This induction required the cytokines interleukin-22 and lymphotoxin in a commensal bacteria-dependent and -independent manner, respectively. Disruption of intestinal fucosylation led to increased susceptibility to infection by Salmonella typhimurium. Our data reveal a role for ILC3 in shaping the gut microenvironment through the regulation of epithelial glycosylation.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Base Sequence
Disease Models, Animal
Fucose / metabolism*
Fucosyltransferases / genetics
Fucosyltransferases / metabolism
Galactoside 2-alpha-L-fucosyltransferase
Germ-Free Life
Glycosylation
Goblet Cells / enzymology
Goblet Cells / immunology
Goblet Cells / microbiology
Ileum / enzymology
Ileum / immunology
Ileum / microbiology
Immunity, Innate*
Interleukin-22
Interleukins / immunology
Intestinal Mucosa / enzymology
Intestinal Mucosa / immunology*
Intestinal Mucosa / microbiology
Lymphocytes / immunology*
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Mutant Strains
Microbiota / immunology*
Molecular Sequence Data
Paneth Cells / enzymology
Paneth Cells / immunology
Paneth Cells / microbiology
Salmonella Infections / immunology*
Salmonella Infections / microbiology
Salmonella typhimurium*

Substances

Interleukins
Fucose
Fucosyltransferases

Associated data

GENBANK/AB470733
GENBANK/AB470734
GENBANK/AB470735
GENBANK/AB470736
GENBANK/AB470737
GENBANK/AB470738
GENBANK/AB470739
GENBANK/AB470740
GENBANK/AB470741
GENBANK/AB470742
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GENBANK/AB470744
GENBANK/AB470745
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GENBANK/AB470750
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GENBANK/AB470765
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GENBANK/AB470811
GENBANK/AB470812
GENBANK/AB470813
GENBANK/AB470814
GENBANK/AB470815

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding