Stat4 isoforms differentially regulate inflammation and demyelination in experimental allergic encephalomyelitis

Caiqing Mo, Wanida Chearwae, John T. O'Malley, Suzanne M. Adams, Saravanan Kanakasabai, Crystal C. Walline, Gretta L. Stritesky, Seth R. Good, Narayanan B. Perumal, Mark H. Kaplan, John J. Bright

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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-γ 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 Stat4β has been characterized that lacks 44 amino acids at the C terminus of the full-length Stat4α. In this study we examined whether T cells expressing either isoform could affect the pathogenesis of EAE. We found that transgenic mice expressing Stat4β on a Stat4-deficient background develop an exacerbated EAE compared with wild-type mice following immunization with myelin oligodendrocyte glycoprotein peptide 35-55, while Stat4α transgenic mice have greatly attenuated disease. The differential development of EAE in transgenic mice correlates with increased IFN-γ and IL-17 in Stat4β-expressing cells in situ, contrasting increased IL-10 production by Stat4α-expressing cells. This study demonstrates that Stat4 isoforms differentially regulate inflammatory cytokines in association with distinct effects on the onset and severity of EAE.

Original languageEnglish (US)
Pages (from-to)5681-5690
Number of pages10
JournalJournal of Immunology
Volume181
Issue number8
DOIs
StatePublished - 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Mo, C., Chearwae, W., O'Malley, J. T., Adams, S. M., Kanakasabai, S., Walline, C. C., Stritesky, G. L., Good, S. R., Perumal, N. B., Kaplan, M. H., & Bright, J. J. (2008). Stat4 isoforms differentially regulate inflammation and demyelination in experimental allergic encephalomyelitis. Journal of Immunology, 181(8), 5681-5690. https://doi.org/10.4049/jimmunol.181.8.5681