| First Author | Martinez NE | Year | 2015 |
| Journal | Brain Behav Immun | Volume | 43 |
| Pages | 86-97 | PubMed ID | 25046854 |
| Mgi Jnum | J:236222 | Mgi Id | MGI:5805421 |
| Doi | 10.1016/j.bbi.2014.07.008 | Citation | Martinez NE, et al. (2015) Th17-biased RORgammat transgenic mice become susceptible to a viral model for multiple sclerosis. Brain Behav Immun 43:86-97 |
| abstractText | 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) gammat, 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 RORgammat 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, RORgammat Tg mice developed inflammatory demyelinating lesions with virus persistence in the spinal cord. TMEV-infected RORgammat Tg mice had higher levels of IL-17, lower levels of interferon-gamma, 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. |
