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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptive Immunity / genetics
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Animals
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism*
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Cell Differentiation / genetics
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Cell Proliferation
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Cells, Cultured
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Lymphocyte Activation / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Mutant Strains
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RNA, Small Interfering / genetics
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Signal Transduction / genetics
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Signal Transduction / immunology
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Sterol Regulatory Element Binding Protein 1 / genetics
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Sterol Regulatory Element Binding Protein 1 / metabolism*
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Sterol Regulatory Element Binding Protein 2 / genetics
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Sterol Regulatory Element Binding Protein 2 / metabolism*
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Transgenes / genetics
Substances
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RNA, Small Interfering
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Srebf1 protein, mouse
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Srebf2 protein, mouse
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Sterol Regulatory Element Binding Protein 1
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Sterol Regulatory Element Binding Protein 2
Associated data
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GEO/GSE44261
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GEO/GSM1081398
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GEO/GSM1081399
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GEO/GSM1081400
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GEO/GSM1081401
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GEO/GSM1081402
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GEO/GSM1081403
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GEO/GSM1081404
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GEO/GSM1081405
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GEO/GSM1081406
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GEO/GSM1081407
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GEO/GSM1081408
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GEO/GSM1081409