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 (Treg cells) in mice. In vitro, D-mannose stimulated Treg cell differentiation in human and mouse cells by promoting TGF-β activation, which in turn was mediated by upregulation of integrin αvβ8 and reactive oxygen species generated by increased fatty acid oxidation. This previously unrecognized immunoregulatory function of D-mannose may have clinical applications for immunopathology.
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This research was supported by the Intramural Research Program of the NIH, NIDCR. We thank E. Shevach (NIAID, NIH, Bethesda, Maryland, USA) for providing the Itgb8f/fCD4-Cre mice, and C. Benoist and D. Mathis (Harvard Medical School, Boston, Massachusetts, USA) for providing the NOD-Foxp3DTR mice. We also thank the NIDCR flow cytometry core for support.
The authors declare no competing financial interests.
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Zhang, D., Chia, C., Jiao, X. et al. D-mannose induces regulatory T cells and suppresses immunopathology. Nat Med 23, 1036–1045 (2017). https://doi.org/10.1038/nm.4375
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