D-mannose induces regulatory T cells and suppresses immunopathology

  • Nat Med. 2017 Sep;23(9):1036-1045. doi: 10.1038/nm.4375.
Dunfang Zhang  1  2 ,  Cheryl Chia  1 ,  Xue Jiao  1  3 ,  Wenwen Jin  1 ,  Shimpei Kasagi  1 ,  Ruiqing Wu  1  2 ,  Joanne E Konkel  1 ,  Hiroko Nakatsukasa  1 ,  Peter Zanvit  1 ,  Nathan Goldberg  1 ,  Qianming Chen  2 ,  Lingyun Sun  4 ,  Zi-Jiang Chen  3 ,  WanJun Chen  1
Affiliations
  • 1. Mucosal Immunology Section, NIDCR, US National Institutes of Health, Bethesda, Maryland, USA.
  • 2. State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Sichuan, China.
  • 3. Center for Reproductive Medicine, Shandong University, Jinan, China.
  • 4. Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
PMID: 28759052 DOI: 10.1038/nm.4375
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-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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