title: Analysis of TGF-β1 and TGF-β3 as regulators of encephalitogenic Th17 cells: Implications for multiple sclerosis.
abstract: The phenotype of the CD4(+) T cells that mediate the CNS pathology in multiple sclerosis is still unclear, and yet a vital question for developing therapies. One of the conundrums is the role of TGF-β in the development of encephalitogenic Th17 cells. In the present study, TGF-β1 and TGF-β3 were directly compared in their capacity to promote the differentiation of myelin-specific Th17 cells that could induce experimental autoimmune encephalomyelitis (EAE). Myelin-specific CD4(+) T cell receptor transgenic cells differentiated with antigen in the presence of IL-6+TGF-β1 or IL-6+TGF-β3 generated T cells that produced robust amounts of IL-17, but were incapable of inducing EAE when transferred into mice. Further analysis of these non-encephalitogenic Th17 cells found that they expressed lower amounts of GM-CSF or IL-23R, both molecules necessary for encephalitogenicity. Thus, TGF-β, irrespective of isoform, negatively regulates the differentiation of encephalitogenic Th17 cells.
authors.affiliation: Molecular Cellular and Developmental Biology Graduate Program, Department of Microbial Infection and Immunity, The Ohio State University, 460 W 12th Ave, Room 660, Columbus, OH, USA. Electronic address: lee.4037@osu.edu.
authors.forename: Priscilla W
authors.initials: PW
authors.lastname: Lee
authors.affiliation: Department of Neurology, The Ohio State University Wexner Medical Center, 460 W 12th Ave, Room 660, Columbus, OH, USA. Electronic address: yuhong.yang@osumc.edu.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurology, Department of Neuroscience, The Ohio State University Wexner Medical Center, 460 W 12th Ave, Room 686, Columbus, OH, USA. Electronic address: michael.racke@osumc.edu.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Racke
authors.affiliation: Department of Microbial Infection and Immunity, Department of Neuroscience, The Ohio State University Wexner Medical Center, Biomedical Research Tower, 460 W 12th Ave, Room 684, Columbus, OH 43210, USA. Electronic address: amy.lovett-racke@osumc.edu.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Lovett-Racke
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D053782:Transforming Growth Factor beta3 / Q000494:pharmacology*
chemical_list: D020381:Interleukin-17; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Experimental autoimmune encephalomyelitis; GM-CSF; IL-23R; Multiple sclerosis; T cell encephalitogenicity; TGF-β1; TGF-β3; Th17 cells