Abstract
The NR4A nuclear receptor family member Nr4a1 is strongly induced in thymocytes undergoing selection, and has been shown to control the development of Treg cells; however the role of Nr4a1 in CD8(+) T cells remains undefined. Here we report a novel role for Nr4a1 in regulating the development and frequency of CD8(+) T cells through direct transcriptional control of Runx3. We discovered that Nr4a1 recruits the corepressor, CoREST to suppress Runx3 expression in CD8(+) T cells. Loss of Nr4a1 results in increased Runx3 expression in thymocytes which consequently causes a 2-fold increase in the frequency and total number of intrathymic and peripheral CD8(+) T cells. Our findings establish Nr4a1 as a novel and critical player in the regulation of CD8 T cell development through the direct suppression of Runx3.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adoptive Transfer
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Animals
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism*
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Cell Differentiation
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Co-Repressor Proteins
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Core Binding Factor Alpha 3 Subunit / genetics*
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Down-Regulation
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Gene Expression Regulation*
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Lymphocyte Count
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Mice
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Mice, Knockout
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Nerve Tissue Proteins / metabolism
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Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics*
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Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism*
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Protein Binding
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Repressor Proteins / metabolism
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Thymus Gland / cytology
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Thymus Gland / immunology
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Transcription, Genetic*
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Transplantation Chimera
Substances
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Co-Repressor Proteins
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Core Binding Factor Alpha 3 Subunit
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Nerve Tissue Proteins
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Nr4a1 protein, mouse
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Nuclear Receptor Subfamily 4, Group A, Member 1
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Rcor2 protein, mouse
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Repressor Proteins