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Sterol regulatory element–binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity
Open accessAbstract
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 (48).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [48]
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Metadata
- 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
- ORCID
- Venue
- Nature Immunology
- Published
- 2013-04-07
- Volume
- 14
- Issue
- 5
- Pages
- 489-499
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC3652626
- 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
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- 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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