SREBPs for T Cell Expansion

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Science  26 Apr 2013:
Vol. 340, Issue 6131, pp. 408
DOI: 10.1126/science.340.6131.408-b

Responding to infections is energetically demanding, especially for cytotoxic CD8+ T cells. Once these cells recognize an infection, they blast, which requires lipid biosynthesis, and then undergo metabolic reprogramming so that they rely primarily on glycolysis to meet their high energetic demands. The specific mechanisms that allow for this transition are not well elucidated. Kidani et al. identify a role for the sterol regulatory element–binding proteins SREBP1 and SREBP2, transcription factors that regulate lipid homeostasis, in this process. The expression of SREBPs is up-regulated in response to T cell activation and is required for the induction of a lipid synthesis program. CD8+ T cells from mice with a T cell–specific deficiency in SREBPs exhibited poor blastogenesis and proliferation upon activation, altered lipid homeostasis, and did not undergo the typical activation-induced metabolic reprogramming. Impaired responses of SREBP-deficient mice to infection with lymphocytic choriomeningitis virus underscored the physiological relevance of this pathway.

Nat. Immunol. 14, 10.1038/ni.2570 (2013).

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