Cited by 552T-cell and B-cell ImmunologyCancer, Lipids, and MetabolismLipid metabolism and biosynthesis

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

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Kidani, Yoko, Elsaesser, Heidi, Hock, M Benjamin, Vergnes, Laurent, Williams, Kevin J, Argus, Joseph P, Marbois, Beth N, Komisopoulou, Evangelia +6 more·2013·Nature Immunology

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.

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  • CD8+ T cells unable to engage acetyl-CoA-dependent lipid biosynthetic pathways display defects in antigen-driven blastogenesis and clonal expansion in response to pathogens.

    “CD8+ T cells unable to engage acetyl-CoA–dependent lipid biosynthetic pathways display defects in antigen-driven blastogenesis and clonal expansion in response to pathogens (48).”

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Authors
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.
Affiliations
  • University of California, Los Angeles (US)
  • Sanford Burnham Prebys Medical Discovery Institute (US)
Corresponding author
Bensinger, Steven J
Venue
Nature Immunology
Published
2013-04-07
Volume
14
Issue
5
Pages
489-499
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
OpenAlex
W2025714915
Cited by
552
References
38
Citations by year
2026: 39 · 2025: 63 · 2024: 55 · 2023: 48 · 2022: 61 · 2021: 52 · 2020: 42 · 2019: 39 · 2018: 29 · 2017: 34 · 2016: 28 · 2015: 32 · 2014: 23 · 2013: 7
FWCI
16.58
Type
journal article
Language
en
Open access
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Heart, Lung, and Blood Institute (P01HL090553, R01HL048044)
  • National Cancer Institute (T32-CA009120-36, T32CA009120)
  • National Institute of General Medical Sciences (T32GM008496, T32-GM008469)
  • National Institute of Allergy and Infectious Diseases (AI093768, U01AI082975, R01AI093768, R01AI085043, AI082975, AI085043)
  • National Center for Research Resources (S10RR026744)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
SREBP, CD8+ T cells, T cell metabolic reprogramming, clonal expansion, T cell blastogenesis, membrane lipid synthesis, homeostatic proliferation, viral infection, adaptive immunity, T cell activation
MeSH terms
Animals, Cell Differentiation, Cells, Cultured, Lymphocyte Activation, Mice, Inbred C57BL, Mice, Mutant Strains, Signal Transduction, CD8-Positive T-Lymphocytes, Transgenes, RNA, Small Interfering, Cell Proliferation, Mice, Sterol Regulatory Element Binding Protein 1, Sterol Regulatory Element Binding Protein 2, Adaptive Immunity

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