title: Induction of gut regulatory CD39+T cells by teriflunomide protects against EAE.
abstract: OBJECTIVE
  To determine whether as an orally delivered treatment, teriflunomide, an inhibitor of the mitochondrial enzyme dihydroorotate dehydrogenase approved to treat relapsing forms of multiple sclerosis, could affect gut-associated lymphoid tissue (GALT) immune responses functionally.
  
  
  METHODS
  C57BL/6 mice were treated orally with teriflunomide and flow cytometric analysis of immune GALT cells performed ex vivo, and adoptive transfer experiments were used to test the protective effects of GALT regulatory T (Treg) cells.
  
  
  RESULTS
  Teriflunomide reduced the percentages of antigen-presenting cells of Peyer patches when compared to controls. Conversely, a significant increase of the relative frequency of CD39+Treg cells was observed. In vivo, the protective effect of GALT-derived teriflunomide-induced CD39+Treg cells was established by adoptive transfer into recipient experimental autoimmune encephalomyelitis mice.
  
  
  CONCLUSIONS
  Our results identify specific GALT-derived CD39+Treg cells as a mechanism of action that may contribute to the efficacy of teriflunomide during CNS inflammatory demyelination and as an oral therapeutic in relapsing multiple sclerosis.
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, NH. J.O.-R. is currently affiliated with the Department of Biology, College of Science, Technology, Engineering and Mathematics, Eastern Washington University, Cheney, WA.
authors.forename: Javier
authors.initials: J
authors.lastname: Ochoa-Repáraz
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, NH. J.O.-R. is currently affiliated with the Department of Biology, College of Science, Technology, Engineering and Mathematics, Eastern Washington University, Cheney, WA.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Colpitts
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, NH. J.O.-R. is currently affiliated with the Department of Biology, College of Science, Technology, Engineering and Mathematics, Eastern Washington University, Cheney, WA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Kircher
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, NH. J.O.-R. is currently affiliated with the Department of Biology, College of Science, Technology, Engineering and Mathematics, Eastern Washington University, Cheney, WA.
authors.forename: Eli J
authors.initials: EJ
authors.lastname: Kasper
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, NH. J.O.-R. is currently affiliated with the Department of Biology, College of Science, Technology, Engineering and Mathematics, Eastern Washington University, Cheney, WA.
authors.forename: Kiel M
authors.initials: KM
authors.lastname: Telesford
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, NH. J.O.-R. is currently affiliated with the Department of Biology, College of Science, Technology, Engineering and Mathematics, Eastern Washington University, Cheney, WA.
authors.forename: Sakhina
authors.initials: S
authors.lastname: Begum-Haque
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, NH. J.O.-R. is currently affiliated with the Department of Biology, College of Science, Technology, Engineering and Mathematics, Eastern Washington University, Cheney, WA.
authors.forename: Anudeep
authors.initials: A
authors.lastname: Pant
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, NH. J.O.-R. is currently affiliated with the Department of Biology, College of Science, Technology, Engineering and Mathematics, Eastern Washington University, Cheney, WA.
authors.forename: Lloyd H
authors.initials: LH
authors.lastname: Kasper