Blimp-1 attenuates Th1 differentiation by repression of ifng, tbx21, and bcl6 gene expression

Luisa Cimmino, Gislaine A. Martins, Jerry Liao, Erna Magnusdottir, Gabriele Grunig, Rocio K. Perez, Kathryn L. Calame

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

T cell-specific deletion of Blimp-1 causes abnormal T cell homeostasis and function, leading to spontaneous, fatal colitis in mice. Herein we explore the role of Blimp-1 in Th1/Th2 differentiation. Blimp-1 mRNA and protein are more highly expressed in Th2 cells compared with Th1 cells, and Blimp-1 attenuates IFN-γ production in CD4 cells activated under nonpolarizing conditions. Although Blimp-1-deficient T cells differentiate normally to Th2 cytokines in vitro, Blimp-1 is required in vivo for normal Th2 humoral responses to NP-KLH (4-hydroxy-3-nitrophenylacetyl/keyhole lymphocyte hemocyanin) immunization. Lack of Blimp-1 in CD4 T cells causes increased IFN-γ, T-bet, and Bcl-6 mRNA. By chromatin immunoprecipitation we show that Blimp-1 binds directly to a distal regulatory region in the ifng gene and at multiple sites in tbx21 and bcl6 genes. Our data provide evidence that Blimp-1 functions in Th2 cells to reinforce Th2 differentiation by repressing critical Th1 genes.

Original languageEnglish (US)
Pages (from-to)2338-2347
Number of pages10
JournalJournal of Immunology
Volume181
Issue number4
DOIs
StatePublished - Aug 15 2008
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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