Abstract
Regulatory T cells (T(reg) cells) are required for peripheral tolerance. Evidence indicates that T(reg) cells can adopt specialized differentiation programs in the periphery that are controlled by transcription factors usually associated with helper T cell differentiation. Here we demonstrate that expression of the transcription factor Blimp-1 defined a population of T(reg) cells that localized mainly to mucosal sites and produced IL-10. Blimp-1 was required for IL-10 production by these cells and for their tissue homeostasis. We provide evidence that the transcription factor IRF4, but not the transcription factor T-bet, was essential for Blimp-1 expression and for the differentiation of all effector T(reg) cells. Thus, our study defines a differentiation pathway that leads to the acquisition of T(reg) cell effector functions and requires both IRF4 and Blimp-1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Binding Sites / genetics
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Cell Differentiation / genetics*
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Cells, Cultured
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Flow Cytometry
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Gene Expression Profiling
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Interferon Regulatory Factors / genetics*
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Interferon Regulatory Factors / metabolism
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Interleukin-10 / genetics
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Interleukin-10 / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Molecular Sequence Data
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Oligonucleotide Array Sequence Analysis
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Positive Regulatory Domain I-Binding Factor 1
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Protein Binding
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Regulatory Sequences, Nucleic Acid / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Homology, Nucleic Acid
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / metabolism*
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Transcription Factors / genetics*
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Transcription Factors / metabolism
Substances
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Interferon Regulatory Factors
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Prdm1 protein, mouse
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Transcription Factors
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interferon regulatory factor-4
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Interleukin-10
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Green Fluorescent Proteins
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Positive Regulatory Domain I-Binding Factor 1