D-mannose induces regulatory T cells and suppresses immunopathology

Dunfang Zhang, Cheryl Chia, Xue Jiao, Wenwen Jin, Shimpei Kasagi, Ruiqing Wu, Joanne E. Konkel, Hiroko Nakatsukasa, Peter Zanvit, Nathan Goldberg, Qianming Chen, Lingyun Sun, Zi Jiang Chen, Wanjun Chen

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32 Citations (Scopus)

Abstract

D-mannose, a C-2 epimer of glucose, exists naturally in many plants and fruits, and is found in human blood at concentrations less than one-fiftieth of that of glucose. However, although the roles of glucose in T cell metabolism, diabetes and obesity are well characterized, the function of D-mannose in T cell immune responses remains unknown. Here we show that supraphysiological levels of D-mannose safely achievable by drinking-water supplementation suppressed immunopathology in mouse models of autoimmune diabetes and airway inflammation, and increased the proportion of Foxp3 + regulatory T cells (T reg cells) in mice. In vitro, D-mannose stimulated T reg cell differentiation in human and mouse cells by promoting TGF-β activation, which in turn was mediated by upregulation of integrin α v β 8 and reactive oxygen species generated by increased fatty acid oxidation. This previously unrecognized immunoregulatory function of D-mannose may have clinical applications for immunopathology.

Original languageEnglish
Pages (from-to)1036-1045
Number of pages10
JournalNature Medicine
Volume23
Issue number9
DOIs
Publication statusPublished - 2017 Sep 1
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Zhang, D., Chia, C., Jiao, X., Jin, W., Kasagi, S., Wu, R., Konkel, J. E., Nakatsukasa, H., Zanvit, P., Goldberg, N., Chen, Q., Sun, L., Chen, Z. J., & Chen, W. (2017). D-mannose induces regulatory T cells and suppresses immunopathology. Nature Medicine, 23(9), 1036-1045. https://doi.org/10.1038/nm.4375