Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
7281407 | Brain, Behavior, and Immunity | 2015 | 12 Pages |
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.
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Authors
Nicholas E. Martinez, Fumitaka Sato, Eiichiro Kawai, Seiichi Omura, Satoru Takahashi, Keigyou Yoh, Ikuo Tsunoda,