Journal
NATURE MEDICINE
Volume 23, Issue 9, Pages 1036-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/nm.4375
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Funding
- Intramural Research Program of the NIH, NIDCR
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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-beta activation, which in turn was mediated by upregulation of integrin alpha(v)beta(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.
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