Journal
JOURNAL OF IMMUNOLOGY
Volume 195, Issue 8, Pages 3515-3519Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1403027
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Funding
- National Institutes of Health [R01HL118765, P01HL055798, F32HL117533-02]
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The transcription factor IFN regulatory factor (IRF) 4 was shown to play a crucial role in the protective CD8(+) T cell response; however, regulation of IRF4 expression in CD8(+) T cells remains unclear. In this article, we report a critical role for Nr4a1 in regulating the expansion, differentiation, and function of CD8(+) T cells through direct transcriptional repression of Irf4. Without Nr4a1, the regulation of IRF4 is lost, driving an increase in Irf4 expression and, in turn, resulting in a faster rate of CD8 T cell proliferation and expansion. Nr4a1-deficient mice show increases in CD8 T cell effector responses with improved clearance of Listeria monocytogenes. Our data support a novel and critical role for Nr4a1 in the regulation of CD8(+) T cell expansion and effector function through transcriptional repression of Irf4.
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