An inhibitory role for the transcription factor Stat3 in controlling IL-4 and Bcl6 expression in follicular helper T cells

Hao Wu, Lin Lin Xu, Paulla Teuscher, Hong Liu, Mark H. Kaplan, Alexander L. Dent

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The transcription factor Bcl6 is required for development of follicular helper T (T<inf>FH</inf>) cells. Cytokines that activate Stat3 promote Bcl6 expression and T<inf>FH</inf> cell differentiation. Previous studies with an acute virus infection model showed that T<inf>FH</inf> cell differentiation was decreased but not blocked in the absence of Stat3. In this study, we further analyzed the role of Stat3 in T<inf>FH</inf> cells. In Peyer's patches, we found that compared with wild-type, Stat3-deficient T<inf>FH</inf> cells developed at a 25% lower rate and expressed increased IFN-γ and IL-4. Whereas Peyer's patch germinal center B cells developed at normal numbers with Stat3-deficient T<inf>FH</inf> cells, IgG1 class switching was greatly increased. Following immunization with sheep RBCs, splenic Stat3-deficient T<inf>FH</inf> cells developed at a slower rate than in control mice, and splenic germinal center B cells were markedly decreased. Stat3-deficient T<inf>FH</inf> cells developed poorly in a competitive bone marrow chimera environment. Under all conditions tested, Stat3-deficient T<inf>FH</inf> cells overexpressed both IL-4 and Bcl6, a pattern specific for the T<inf>FH</inf> cell population. Finally, we found in vitro that repression of IL-4 expression in CD4 T cells by Bcl6 required Stat3 function. Our data indicate that Stat3 can repress the expression of Bcl6 and IL-4 in T<inf>FH</inf> cells, and that Stat3 regulates the ability of Bcl6 to repress target genes. Overall, we conclude that Stat3 is required to fine-tune the expression of multiple key genes in T<inf>FH</inf> cells, and that the specific immune environment determines the function of Stat3 in T<inf>FH</inf> cells.

Original languageEnglish (US)
Pages (from-to)2080-2089
Number of pages10
JournalJournal of Immunology
Volume195
Issue number5
DOIs
StatePublished - Sep 1 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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