D-mannose induces regulatory T cells and suppresses immunopathology.

Nature medicine 2017 Sep

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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 (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.

Citation

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. D-mannose induces regulatory T cells and suppresses immunopathology. Nature medicine. 2017 Sep;23(9):1036-1045