CCAAT/enhancer-binding protein α negatively regulates IFN-γ expression in T cells

Shinya Tanaka, Kentaro Tanaka, Fay Magnusson, Yeonseok Chung, Gustavo J. Martinez, Yi Hong Wang, Roza I. Nurieva, Tomohiro Kurosaki, Chen Dong

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Humoral immunity, including Ab switching and somatic hypermutation, is critically regulated by CD4+ T cells. T follicular helper (Tfh) cells have been recently shown to be a distinct T cell subset important in germinal center reactions. The transcriptional regulation of Tfh cell development and function has not been well understood. In this study, we report that C/EBPα, a basic region/leucine zipper transcription factor, is highly expressed in Tfh cells. Cebpa-deficient CD4+ T cells exhibit enhanced IFN-γ expression in vitro and in vivo. T cell-specific Cebpa knockout mice, although not defective in Tfh cell generation, produce significantly increased levels of IgG2a/b and IgG3 following immunization with a protein Ag. Moreover, C/EBPα binds to the Ifng gene and inhibits T-bet-driven Ifng transcription in a DNA binding-dependent manner. Our study thus demonstrates that C/EBPα restricts IFN-γ expression in T cells to allow proper class switching by B cells.

Original languageEnglish
Pages (from-to)6152-6160
Number of pages9
JournalJournal of Immunology
Volume193
Issue number12
DOIs
Publication statusPublished - Dec 15 2014

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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