imprint:
Springer Science and Business Media LLC, 2016
Published in:
Scientific Reports, 6 (2016) 1
Language:
English
DOI:
10.1038/srep35521
ISSN:
2045-2322
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title><jats:p>The transcription factor Interferon Regulatory Factor 4 (IRF4) is essential for T<jats:sub>H2</jats:sub> and T<jats:sub>H17</jats:sub> cell formation and controls peripheral CD8<jats:sup>+</jats:sup> T cell differentiation. We used <jats:italic>Listeria monocytogenes</jats:italic> infection to characterize the function of IRF4 in T<jats:sub>H1</jats:sub> responses. IRF4<jats:sup>−/−</jats:sup> mice generated only marginal numbers of listeria-specific T<jats:sub>H1</jats:sub> cells. After transfer into infected mice, IRF4<jats:sup>−/−</jats:sup> CD4<jats:sup>+</jats:sup> T cells failed to differentiate into T<jats:sub>H1</jats:sub> cells as indicated by reduced T-bet and IFN-γ expression, and showed limited proliferation. Activated IRF4<jats:sup>−/−</jats:sup> CD4<jats:sup>+</jats:sup> 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<jats:sub>H1</jats:sub> differentiation of IRF4<jats:sup>−/−</jats:sup> CD4<jats:sup>+</jats:sup> T cells. Our study identifies IRF4 as central regulator of T<jats:sub>H1</jats:sub> responses and cellular metabolism. We propose that this function of IRF4 is fundamental for the initiation and maintenance of all T<jats:sub>H</jats:sub> cell responses.</jats:p>