Nature Medicine
Nature Medicine
5 years ago

D-mannose induces regulatory T cells and suppresses immunopathology

D-mannose induces regulatory T cells and suppresses immunopathology
Qianming Chen, Zi-Jiang Chen, Wenwen Jin, WanJun Chen, Peter Zanvit, Dunfang Zhang, Lingyun Sun, Nathan Goldberg, Shimpei Kasagi, Joanne E Konkel, Cheryl Chia, Hiroko Nakatsukasa, Ruiqing Wu, Xue Jiao
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.

Publisher URL: http://dx.doi.org/10.1038/nm.4375

DOI: 10.1038/nm.4375

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