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The influence of gut-derived CD39 regulatory T cells in CNS demyelinating disease

      There is considerable interest in trying to understand the importance of the gut microbiome in human diseases. The association between dysbiosis, an altered microbial composition, as related to human disease is being explored in the context of different autoimmune conditions, including multiple sclerosis (MS). Recent studies suggest that MS affects the composition of the gut microbiota by altering the relative abundances of specific bacteria and archaea species. Remarkably, some of the bacterial species shown reduced in the gut of MS patients are known to promote immunosuppressive regulatory T cells (Tregs). In MS, the function of a phenotype of Tregs that express CD39, an ectoenzyme involved in the catabolism of adenosine triphosphate as immunomodulatory cells, appears to be reduced. In this review, we discuss the involvement of the gut microbiota in the regulation of experimental models of central nervous system inflammatory demyelination and review the evidence that link the gut microbiome with MS. Further, we hypothesize that the gut microbiome is an essential organ for the control of tolerance in MS patients and a potential source for safer novel therapeutics.

      Abbreviations:

      APC (antigen presenting cell), ATP (adenosine triphosphate), ASDs (autism spectrum disorders), BBB (blood–brain barrier), CNS (central nervous system), CSF (cerebrospinal fluid), EAE (experimental autoimmune or allergic encephalomyelitis), Foxp3 (Fork-head box 3), GALT (gut-associated lymphoid tissues), IFN-γ (Interferon gamma), IL (Interleukin), LPS (lipopolysaccharide), MS (multiple sclerosis), PBMC (peripheral mononuclear cell), PSA (polysaccharide A), RR-MS (relapsing-remitting multiple sclerosis), SCFA (short-chain fatty acids), TGF-β (tumor growth factor beta), Th cell (T helper cell), TLR (toll-like receptor), TNF-α (tumor necrosis factor alpha), Tregs (regulatory T cells)
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