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Nat Med. 2017 Sep;23(9):1036-1045. doi: 10.1038/nm.4375. Epub 2017 Jul 24.

D-mannose induces regulatory T cells and suppresses immunopathology.

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Mucosal Immunology Section, NIDCR, US National Institutes of Health, Bethesda, Maryland, USA.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Sichuan, China.
Center for Reproductive Medicine, Shandong University, Jinan, China.
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.


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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