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Oral D-mannose treatment suppresses experimental autoimmune encephalomyelitis via induction of regulatory T cells

Published:November 17, 2021DOI:https://doi.org/10.1016/j.jneuroim.2021.577778

      Highlights

      • D-mannose (D-m) is a naturally occurring epimer of glucose with known immunoregulatory properties.
      • D-m treatment suppressed both chronic and relapsing-remitting experimental autoimmune encephalomyelitis (EAE).
      • Treatment with D-m reduced numbers of immune cells in the brain and spinal cord of mice with EAE.
      • There was a reduction in numbers of myeloid cells present in the central nervous system (CNS) of mice with EAE treated with D-m.
      • D-m treatment increased the frequency of regulatory T (Treg) cells in the CNS, suggesting a Treg dependent mechanism.

      Abstract

      D-mannose (D-m) is a glucose epimer found in natural products, especially fruits. In mouse models of diabetes and airway inflammation, D-m supplementation via drinking water attenuated pathology by modifying cellular energy metabolism, leading to the activation of latent transforming growth factor beta (TGF-β), which in turn induced T regulatory cells (Tregs). Given that Tregs are important in controlling neuroinflammation in experimental autoimmune encephalomyelitis (EAE) and likely in multiple sclerosis (MS), we hypothesized that D-m could also suppress EAE. We found that D-m delayed disease onset and reduced disease severity in two models of EAE. Importantly, D-m treatment prevented relapses in a relapsing-remitting model of EAE, which mimics the most common clinical manifestation of MS. EAE suppression was accompanied by increased frequency of CD4+FoxP3+ Tregs in the central nervous system, suggesting that EAE suppression resulted from Treg cell induction by D-m. These findings suggest that D-m has the potential to be a safe and low-cost complementary therapy for MS.

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