Sterol regulatory element-binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity

Yoko Kidani, Heidi Elsaesser, M. Benjamin Hock, Laurent Vergnes, Kevin J. Williams, Joseph P. Argus, Beth N. Marbois, Evangelia Komisopoulou, Elizabeth B. Wilson, Timothy F. Osborne, Thomas G. Graeber, Karen Reue, David G. Brooks, Steven J. Bensinger

Research output: Contribution to journalArticle

Abstract

Newly activated CD8+ T cells reprogram their metabolism to meet the extraordinary biosynthetic demands of clonal expansion; however, the signals that mediate metabolic reprogramming remain poorly defined. Here we demonstrate an essential role for sterol regulatory element-binding proteins (SREBPs) in the acquisition of effector-cell metabolism. Without SREBP signaling, CD8 + T cells were unable to blast, which resulted in attenuated clonal expansion during viral infection. Mechanistic studies indicated that SREBPs were essential for meeting the heightened lipid requirements of membrane synthesis during blastogenesis. SREBPs were dispensable for homeostatic proliferation, which indicated a context-specific requirement for SREBPs in effector responses. Our studies provide insights into the molecular signals that underlie the metabolic reprogramming of CD8+ T cells during the transition from quiescence to activation.

Original languageEnglish (US)
Pages (from-to)489-499
Number of pages11
JournalNature Immunology
Volume14
Issue number5
DOIs
StatePublished - May 1 2013

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Kidani, Y., Elsaesser, H., Hock, M. B., Vergnes, L., Williams, K. J., Argus, J. P., Marbois, B. N., Komisopoulou, E., Wilson, E. B., Osborne, T. F., Graeber, T. G., Reue, K., Brooks, D. G., & Bensinger, S. J. (2013). Sterol regulatory element-binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity. Nature Immunology, 14(5), 489-499. https://doi.org/10.1038/ni.2570