title: RORγt, but not T-bet, overexpression exacerbates an autoimmune model for multiple sclerosis.
abstract: Th17 cells play an important role in multiple sclerosis (MS) and its autoimmune model, experimental autoimmune encephalomyelitis (EAE). However, studies have not addressed how enhanced Th17 immune responses can affect demyelinating diseases. We induced EAE with MOG in RORγt transgenic C57BL/6 mice that overexpress a Th17 inducing transcription factor. RORγt transgenic mice developed more severe EAE than wild-type mice with more robust anti-MOG Th17 immune responses. In contrast, mice overexpressing T-bet, a Th1-inducing transcription factor, were resistant to EAE. Therefore, a genetic bias toward Th17 immune responses could contribute to CNS immunopathology.
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Martinez
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Sato
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Omura
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Kawai
authors.affiliation: Department of Anatomy and Embryology, Faculty of Medicine, International Institute for Integrative Sleep Medicine (WPI-IIIS), Life Science Center, Tsukuba Research Alliance (TARA), Laboratory Animal Resource Center (LARC), University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Nephrology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan.
authors.forename: Keigyou
authors.initials: K
authors.lastname: Yoh
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. Electronic address: itsuno@lsuhsc.edu.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Tsunoda
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics; D005434:Flow Cytometry; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics*; D020825:T-Box Domain Proteins / Q000235:genetics; D018417:Th1 Cells / Q000473:pathology; D000098815:T-bet Transcription Factor
chemical_list: D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor
keywords: Autoimmune disease; Demyelinating disease; Gain-of-function; Genetic association; T cell differentiation