| First Author | Mo C | Year | 2008 |
| Journal | J Immunol | Volume | 181 |
| Issue | 8 | Pages | 5681-90 |
| PubMed ID | 18832727 | Mgi Jnum | J:140753 |
| Mgi Id | MGI:3814504 | Doi | 10.4049/jimmunol.181.8.5681 |
| Citation | Mo C, et al. (2008) Stat4 isoforms differentially regulate inflammation and demyelination in experimental allergic encephalomyelitis. J Immunol 181(8):5681-90 |
| abstractText | Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease model of multiple sclerosis. Signal transducer and activator of transcription 4 (Stat4) is a transcription factor activated by IL-12 and IL-23, two cytokines known to play important roles in the pathogenesis of EAE by inducing T cells to secrete IFN-gamma and IL-17, respectively. We and others have previously shown that therapeutic intervention or targeted disruption of Stat4 was effective in ameliorating EAE. Recently, a splice variant of Stat4 termed Stat4beta has been characterized that lacks 44 amino acids at the C terminus of the full-length Stat4alpha. In this study we examined whether T cells expressing either isoform could affect the pathogenesis of EAE. We found that transgenic mice expressing Stat4beta on a Stat4-deficient background develop an exacerbated EAE compared with wild-type mice following immunization with myelin oligodendrocyte glycoprotein peptide 35-55, while Stat4alpha transgenic mice have greatly attenuated disease. The differential development of EAE in transgenic mice correlates with increased IFN-gamma and IL-17 in Stat4beta-expressing cells in situ, contrasting increased IL-10 production by Stat4alpha-expressing cells. This study demonstrates that Stat4 isoforms differentially regulate inflammatory cytokines in association with distinct effects on the onset and severity of EAE. |
