d-mannose induces regulatory T cells and suppresses immunopathology by WanJun Chen from the Mucosal Immunology Section of NIH Funded by NIH Abstract: 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-b activation, which in turn was mediated by upregulation of integrin avb8 and reactive oxygen species generated by increased fatty acid oxidation. This previously unrecognized immunoregulatory function of d-mannose may have clinical applications for immunopathology.