CCAAT/enhancer-binding Protein α Negatively Regulates IFN-γ Expression in T Cells

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2014 Nov 16

PMID 25398328

Citations 10

Authors

Shinya Tanaka

Kentaro Tanaka

Fay Magnusson

Yeonseok Chung

Gustavo J Martinez

Yi-Hong Wang

Roza I Nurieva

Tomohiro Kurosaki

Chen Dong

Affiliations

Soon will be listed here.

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.

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