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 journalArticle

4 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

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CCAAT-Enhancer-Binding Proteins
Helper-Inducer T-Lymphocytes
T-Lymphocytes
Basic-Leucine Zipper Transcription Factors
Immunoglobulin Class Switching
Germinal Center
T-Lymphocyte Subsets
Humoral Immunity
Knockout Mice
Immunization
B-Lymphocytes
Immunoglobulin G
DNA
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Tanaka, S., Tanaka, K., Magnusson, F., Chung, Y., Martinez, G. J., Wang, Y. H., ... Dong, C. (2014). CCAAT/enhancer-binding protein α negatively regulates IFN-γ expression in T cells. Journal of Immunology, 193(12), 6152-6160. https://doi.org/10.4049/jimmunol.1303422

CCAAT/enhancer-binding protein α negatively regulates IFN-γ expression in T cells. / Tanaka, Shinya; Tanaka, Kentaro; Magnusson, Fay; Chung, Yeonseok; Martinez, Gustavo J.; Wang, Yi Hong; Nurieva, Roza I.; Kurosaki, Tomohiro; Dong, Chen.

In: Journal of Immunology, Vol. 193, No. 12, 15.12.2014, p. 6152-6160.

Research output: Contribution to journalArticle

Tanaka, S, Tanaka, K, Magnusson, F, Chung, Y, Martinez, GJ, Wang, YH, Nurieva, RI, Kurosaki, T & Dong, C 2014, 'CCAAT/enhancer-binding protein α negatively regulates IFN-γ expression in T cells', Journal of Immunology, vol. 193, no. 12, pp. 6152-6160. https://doi.org/10.4049/jimmunol.1303422
Tanaka, Shinya ; Tanaka, Kentaro ; Magnusson, Fay ; Chung, Yeonseok ; Martinez, Gustavo J. ; Wang, Yi Hong ; Nurieva, Roza I. ; Kurosaki, Tomohiro ; Dong, Chen. / CCAAT/enhancer-binding protein α negatively regulates IFN-γ expression in T cells. In: Journal of Immunology. 2014 ; Vol. 193, No. 12. pp. 6152-6160.
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