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Epithelial glycosylation in gut homeostasis and inflammation

Nature Immunology volume 17, pages 1244–1251 (2016)Cite this article

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Abstract

Intestinal epithelial cells apically express glycans, especially α1,2-fucosyl linkages, which work as a biological interface for the host–microbe interaction. Emerging studies have shown that epithelial α1,2-fucosylation is regulated by microbes and by group 3 innate lymphoid cells (ILC3s). Dysregulation of the gene (FUT2) encoding fucosyltransferase 2, an enzyme governing epithelial α1,2-fucosylation, is associated with various human disorders, including infection and chronic inflammatory diseases. This suggests a critical role for an interaction between microbes, epithelial cells and ILC3s mediated via glycan residues. In this Review, using α1,2-fucose and Fut2 gene expression as an example, we describe how epithelial glycosylation is controlled by immune cells and luminal microbes. We also address the pathophysiological contribution of epithelial α1,2-fucosylation to pathogenic and commensal microbes as well as the potential of α1,2-fucose and its regulatory pathway as previously unexploited targets in the development of new therapeutic approaches for human diseases.

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Figure 1: Intestinal epithelial α1,2-fucose synthesized by fucosyltransferases is a symbiotic molecule between host and microbes.
Figure 2: Intestinal epithelial α1,2-fucosylation is regulated by bacterial signals and immune cells.
Figure 3: Biological trade-off mediated by epithelial α1,2-fucose.

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Acknowledgements

This work is financially supported by the Core Research for Evolutional Science and Technology Program of the Japan Science and Technology Agency (JSPS; to H.K.); a Grant-in-Aid for Scientific Research on Innovative Areas (Homeostatic regulation by various types of cell death) (15H01367 to S.U.); a Scientific Research (S) grant (23229004 to H.K.); a Research Activity Start-up grant (15H06159 to Y.G.); a Young Scientists (A) grant (16H06229 to Y.G.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; a Challenging Exploratory Research grant from the JSPS (to S.U.); a grant (Adjuvant database) from The Ministry of Health, Labor and Welfare (MHLW) and the Japan Agency for Medical Research and Development (AMED) (to S.U. and H.K.); The Uehara Memorial Foundation (to Y.G.); The Naito Foundation (to Y.G.); the Astellas Foundation for Research on Metabolic Disorders (to Y.G.); and the Takeda Science Foundation (to Y.G.).

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Authors and Affiliations

  1. Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, Japan

    Yoshiyuki Goto

  2. International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Yoshiyuki Goto, Satoshi Uematsu & Hiroshi Kiyono

  3. Department of Mucosal Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan

    Satoshi Uematsu

  4. Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan

    Hiroshi Kiyono

  5. Division of Mucosal Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Hiroshi Kiyono

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Goto, Y., Uematsu, S. & Kiyono, H. Epithelial glycosylation in gut homeostasis and inflammation. Nat Immunol 17, 1244–1251 (2016). https://doi.org/10.1038/ni.3587

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