TY - JOUR
T1 - CCAAT/enhancer-binding protein α negatively regulates IFN-γ expression in T cells
AU - Tanaka, Shinya
AU - Tanaka, Kentaro
AU - Magnusson, Fay
AU - Chung, Yeonseok
AU - Martinez, Gustavo J.
AU - Wang, Yi Hong
AU - Nurieva, Roza I.
AU - Kurosaki, Tomohiro
AU - Dong, Chen
N1 - Publisher Copyright:
Copyright © 2014 by The American Association of Immunologists, Inc.
PY - 2014/12/15
Y1 - 2014/12/15
N2 - 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.
AB - 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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U2 - 10.4049/jimmunol.1303422
DO - 10.4049/jimmunol.1303422
M3 - Article
C2 - 25398328
AN - SCOPUS:84916898042
SN - 0022-1767
VL - 193
SP - 6152
EP - 6160
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -