STAT4 isoforms differentially regulate Th1 cytokine production and the severity of inflammatory bowel disease

John T. O'Malley, Rajaraman D. Eri, Gretta L. Stritesky, Anubhav N. Mathur, Hua Chen Chang, Harm HogenEsch, Mythily Srinivasan, Mark Kaplan

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

STAT4, a critical regulator of inflammation in vivo, can be expressed as two alternative splice forms, a full-length STAT4α, and a STAT4β isoform lacking a C-terminal transactivation domain. Each isoform is sufficient to program Th1 development through both common and distinct subsets of target genes. However, the ability of these isoforms to mediate inflammation in vivo has not been examined. Using a model of colitis that develops following transfer of CD4+ CD45RBhigh T cells expressing either the STAT4α or STAT4β isoform into SCID mice, we determined that although both isoforms mediate inflammation and weight loss, STAT4β promotes greater colonic inflammation and tissue destruction. This correlates with STAT4 isoform-dependent expression of TNF-α and GM-CSF in vitro and in vivo, but not Th1 expression of IFN-γ or Th17 expression of IL-17, which were similar in STAT4α- and STAT4β-expressing T cells. Thus, higher expression of a subset of inflammatory cytokines from STAT4β-expressing T cells correlates with the ability of STAT4β-expressing T cells to mediate more severe inflammatory disease.

Original languageEnglish
Pages (from-to)5062-5070
Number of pages9
JournalJournal of Immunology
Volume181
Issue number7
StatePublished - Oct 1 2008

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Inflammatory Bowel Diseases
Protein Isoforms
Cytokines
Inflammation
T-Lymphocytes
SCID Mice
Interleukin-17
Colitis
Granulocyte-Macrophage Colony-Stimulating Factor
Transcriptional Activation
Weight Loss
Genes

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

STAT4 isoforms differentially regulate Th1 cytokine production and the severity of inflammatory bowel disease. / O'Malley, John T.; Eri, Rajaraman D.; Stritesky, Gretta L.; Mathur, Anubhav N.; Chang, Hua Chen; HogenEsch, Harm; Srinivasan, Mythily; Kaplan, Mark.

In: Journal of Immunology, Vol. 181, No. 7, 01.10.2008, p. 5062-5070.

Research output: Contribution to journalArticle

O'Malley, John T. ; Eri, Rajaraman D. ; Stritesky, Gretta L. ; Mathur, Anubhav N. ; Chang, Hua Chen ; HogenEsch, Harm ; Srinivasan, Mythily ; Kaplan, Mark. / STAT4 isoforms differentially regulate Th1 cytokine production and the severity of inflammatory bowel disease. In: Journal of Immunology. 2008 ; Vol. 181, No. 7. pp. 5062-5070.
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AU - Chang, Hua Chen

AU - HogenEsch, Harm

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