期刊
JOURNAL OF IMMUNOLOGY
卷 181, 期 8, 页码 5681-5690出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.8.5681
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资金
- National Institutes of Health [R01 NS42257, A1045515]
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 Stat4 beta has been characterized that lacks 44 amino acids at the C terminus of the full-length Stat4 alpha. In this study we examined whether T cells expressing either isoform could affect the pathogenesis of EAE. We found that transgenic mice expressing Stat4 beta on a Stat4-deficient background develop an exacerbated EAE compared with wild-type mice following immunization with myelin oligodendrocyte glycoprotein peptide 35-55, while Stat4 alpha transgenic mice have greatly attenuated disease. The differential development of EAE in transgenic mice correlates with increased IFN-gamma and IL-17 in Stat4 beta-expressing cells in situ, contrasting increased IL-10 production by Stat4 alpha-expressing cells. This study demonstrates that Stat4 isoforms differentially regulate inflammatory cytokines in association with distinct effects on the onset and severity of EAE.
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