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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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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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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DOI: https://doi.org/10.1038/ni.3587
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