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

First Author  Tanaka S Year  2014
Journal  J Immunol Volume  193
Issue  12 Pages  6152-60
PubMed ID  25398328 Mgi Jnum  J:324537
Mgi Id  MGI:6859072 Doi  10.4049/jimmunol.1303422
Citation  Tanaka S, et al. (2014) CCAAT/enhancer-binding protein alpha negatively regulates IFN-gamma expression in T cells. J Immunol 193(12):6152-60
abstractText  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/EBPalpha, a basic region/leucine zipper transcription factor, is highly expressed in Tfh cells. Cebpa-deficient CD4(+) T cells exhibit enhanced IFN-gamma 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/EBPalpha binds to the Ifng gene and inhibits T-bet-driven Ifng transcription in a DNA binding-dependent manner. Our study thus demonstrates that C/EBPalpha restricts IFN-gamma expression in T cells to allow proper class switching by B cells.
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