Interferon Regulatory Factor 4 controls T cell effector function and metabolism.

The transcription factor Interferon Regulatory Factor 4 (IRF4) is essential for T and T cell formation and controls peripheral CD8 T cell differentiation. We used Listeria monocytogenes infection to characterize the function of IRF4 in T responses. IRF4 mice generated only marginal numbers of listeria-specific T cells. After transfer into infected mice, IRF4 CD4 T cells failed to differentiate into T cells as indicated by reduced T-bet and IFN-γ expression, and showed limited proliferation. Activated IRF4 CD4 T cells exhibited diminished uptake of the glucose analog 2-NBDG, limited oxidative phosphorylation and strongly reduced aerobic glycolysis. Insufficient metabolic adaptation contributed to the limited proliferation and T differentiation of IRF4 CD4 T cells. Our study identifies IRF4 as central regulator of T responses and cellular metabolism. We propose that this function of IRF4 is fundamental for the initiation and maintenance of all T cell responses.