Abstract
The transcription factors T-bet and Bcl-6 are required for the establishment of a T helper type 1 cell (T(H)1 cell) and follicular helper T cell (T(FH) cell) gene-expression profile, respectively. Here we found that high concentrations of interleukin 2 (IL-2) inhibited Bcl-6 expression in polarized T(H)1 cells. Mechanistically, the low concentrations of Bcl-6 normally found in effector T(H)1 cells did not repress its target genes because a T-bet-Bcl-6 complex masked the Bcl-6 DNA-binding domain. T(H)1 cells increased their Bcl-6/T-bet ratio in response to limiting IL-2 conditions, which allowed excess Bcl-6 to repress its direct target Prdm1 (which encodes the transcriptional repressor Blimp-1). The Bcl-6-dependent repression of Blimp-1 effectively induced a partial T(FH) profile because Blimp-1 directly repressed a subset of T(FH) signature genes, including Cxcr5. Thus, IL-2-signaling regulates the Bcl-6-Blimp-1 axis in T(H)1 cells to maintain flexibility with a T(FH) cell-like gene profile.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / genetics*
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Cell Differentiation / immunology
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Cells, Cultured
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Gene Expression Profiling
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Gene Expression Regulation / immunology*
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Immunoblotting
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Immunoprecipitation
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Oligonucleotide Array Sequence Analysis
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Positive Regulatory Domain I-Binding Factor 1
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Proto-Oncogene Proteins c-bcl-6 / genetics*
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Proto-Oncogene Proteins c-bcl-6 / immunology
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Proto-Oncogene Proteins c-bcl-6 / metabolism
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Real-Time Polymerase Chain Reaction
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Signal Transduction / genetics
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Signal Transduction / immunology
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T-Box Domain Proteins / genetics
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T-Box Domain Proteins / metabolism
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / immunology
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Th1 Cells / cytology*
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Th1 Cells / immunology
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Transcription Factors / genetics
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Transcription Factors / immunology
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Transcription Factors / metabolism
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Transfection
Substances
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Prdm1 protein, mouse
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Proto-Oncogene Proteins c-bcl-6
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Transcription Factors
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Positive Regulatory Domain I-Binding Factor 1