title: Th17-biased RORγt transgenic mice become susceptible to a viral model for multiple sclerosis.
abstract: In a viral model for multiple sclerosis (MS), Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), both immune-mediated tissue damage (immunopathology) and virus persistence have been shown to cause pathology. T helper (Th) 17 cells are a Th cell subset, whose differentiation requires the transcription factor retinoic acid-related orphan receptor (ROR) γt, secrete pro-inflammatory cytokines, including IL-17, and can antagonize Th1 cells. Although Th17 cells have been shown to play a pathogenic role in immune-mediated diseases or a protective role in bacterial and fungal infections, their role in viral infections is unclear. Using newly established Th17-biased RORγt Tg mice, we tested whether Th17 cells could play a pathogenic or protective role in TMEV-IDD by contributing to immunopathology and/or by modulating anti-viral Th1 immune responses. While TMEV-infected wild-type littermate C57BL/6 mice are resistant to TMEV-IDD, RORγt Tg mice developed inflammatory demyelinating lesions with virus persistence in the spinal cord. TMEV-infected RORγt Tg mice had higher levels of IL-17, lower levels of interferon-γ, and fewer CD8(+) T cells, without alteration in overall levels of anti-viral lymphoproliferative and antibody responses, compared with TMEV-infected wild-type mice. This suggests that a Th17-biased "gain-of-function" mutation could increase susceptibility to virus-mediated demyelinating diseases.
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: Eiichiro
authors.initials: E
authors.lastname: Kawai
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 Anatomy and Embryology, Faculty of Medicine, International Institute for Integrative Sleep Medicine (WPI-IIIS), Life Science Center of Tsukuba Advanced Research Alliance (TARA), Laboratory Animal Resource Center (LARC), University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Anatomy and Embryology, Faculty of Medicine, International Institute for Integrative Sleep Medicine (WPI-IIIS), Life Science Center of Tsukuba Advanced Research Alliance (TARA), Laboratory Animal Resource Center (LARC), University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305, 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; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D051379:Mice; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D013116:Spinal Cord / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology*; D017945:Theilovirus / Q000276:immunology*
keywords: CD8-positive lymphocytes; CNS disease; Demyelinating disease; Disease susceptibility; Inflammation; Picornaviridae; Viral CNS infections