Cutting Edge: The Orphan Nuclear Receptor Nr4a1 Regulates CD8+ T Cell Expansion and Effector Function through Direct Repression of Irf4

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.