CCAAT/enhancer-binding protein α negatively regulates IFN-γ expression in T cells.
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.
Department of Immunology and Center for Inflammation and Cancer, MD Anderson Cancer Center, Houston, TX 77054; Laboratory of Lymphocyte Differentiation, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; and.
Shinya
S
Tanaka
Department of Immunology and Center for Inflammation and Cancer, MD Anderson Cancer Center, Houston, TX 77054;
Kentaro
K
Tanaka
Department of Immunology and Center for Inflammation and Cancer, MD Anderson Cancer Center, Houston, TX 77054;
Fay
F
Magnusson
Department of Immunology and Center for Inflammation and Cancer, MD Anderson Cancer Center, Houston, TX 77054;
Yeonseok
Y
Chung
Department of Immunology and Center for Inflammation and Cancer, MD Anderson Cancer Center, Houston, TX 77054;
Gustavo J
GJ
Martinez
Department of Immunology and Center for Inflammation and Cancer, MD Anderson Cancer Center, Houston, TX 77054;
Yi-hong
YH
Wang
Department of Immunology and Center for Inflammation and Cancer, MD Anderson Cancer Center, Houston, TX 77054;
Roza I
RI
Nurieva
Laboratory of Lymphocyte Differentiation, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; and.
Tomohiro
T
Kurosaki
Department of Immunology and Center for Inflammation and Cancer, MD Anderson Cancer Center, Houston, TX 77054; Institute for Immunology, Tsinghua University, Beijing 100084, China chendong@tsinghua.edu.cn.
Chen
C
Dong
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D056724:Immunity, Humoral; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020825:T-Box Domain Proteins / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic; D000098815:T-bet Transcription Factor
D022763:CCAAT-Enhancer-Binding Protein-alpha; C573415:IFNG protein, human; D007074:Immunoglobulin G; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma