The DOI matches its Crossref record; 77 of the 78 references it cites were found in a registry or an index.
Metabolic reprogramming of human CD8+ memory T cells through loss of SIRT1
Open accessAbstract
The expansion of CD8+CD28– T cells, a population of terminally differentiated memory T cells, is one of the most consistent immunological changes in humans during aging. CD8+CD28– T cells are highly cytotoxic, and their frequency is linked to many age-related diseases. As they do not accumulate in mice, many of the molecular mechanisms regulating their fate and function remain unclear. In this paper, we find that human CD8+CD28– T cells, under resting conditions, have an enhanced capacity to use glycolysis, a function linked to decreased expression of the NAD+-dependent protein deacetylase SIRT1. Global gene expression profiling identified the transcription factor FoxO1 as a SIRT1 target involved in transcriptional reprogramming of CD8+CD28– T cells. FoxO1 is proteasomally degraded in SIRT1-deficient CD8+CD28– T cells, and inhibiting its activity in resting CD8+CD28+ T cells enhanced glycolytic capacity and granzyme B production as in CD8+CD28– T cells. These data identify the evolutionarily conserved SIRT1–FoxO1 axis as a regulator of resting CD8+ memory T cell metabolism and activity in humans.
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“This cell population is characterized by decreased SIRT1 and FOXO1 levels, resulting in an enhanced glycolytic capacity and granzyme B production116.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [116]
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Cites
Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855
Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
Sallusto, F., Lenig, D., Förster, R., Lipp, M., & Lanzavecchia, A. (1999) · Nature · doi:10.1038/44385 · Cited by 5,846 · cited 5×
“Down-regulated genes included CD28 and previously reported T cell homing receptors, such as C-C chemokine receptor type 7 (CCR7) and l-selectin (CD62L), as well as long-term survival cytokine receptor IL7R (Fig.”
BackgroundInfluentialStress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., Greer, P. L., Lin, Y., Tran, H., Ross, S. E., Mostoslavsky, R., Cohen, H. Y., et al. (2004) · Science · doi:10.1126/science.1094637 · Cited by 3,239
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“Enhancing the expression of the ancestral SIR2 protein in yeast and worms promotes organismal life span extension (Kaeberlein et al., 1999; Tissenbaum and Guarente, 2001).”
BackgroundPosttranscriptional Control of T Cell Effector Function by Aerobic Glycolysis
Chang, C.-H., Curtis, J. D., Maggi, L. B., Faubert, B., Villarino, A. V., O’Sullivan, D., Huang, S. C.-C., van der Windt, G. J. W., Blagih, J., Qiu, J., et al. (2013) · Cell · doi:10.1016/j.cell.2013.05.016 · Cited by 2,204
Sirtuins as regulators of metabolism and healthspan
Houtkooper, R. H., Pirinen, E., & Auwerx, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3293 · Cited by 2,008
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Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
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Phenotypic and functional separation of memory and effector human CD8+ T cells
Hamann, D., Baars, P. A., Rep, M. H. G., Hooibrink, B., Kerkhof-Garde, S. R., Klein, M. R., & Lier, R. A. W. V. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.9.1407 · Cited by 1,366
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NAD+ metabolism and its roles in cellular processes during ageing
Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00313-x · Cited by 1,617
Self-citationMechanisms underlying T cell ageing
Goronzy, J. J., & Weyand, C. M. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0180-1 · Cited by 506
SIRT1 is downregulated by autophagy in senescence and ageing
Xu, C., Wang, L., Fozouni, P., Evjen, G., Chandra, V., Jiang, J., Lu, C., Nicastri, M. C., Bretz, C. L., Winkler, J. D., et al. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-00579-5 · Cited by 478
Self-citationMetabolic signaling in T cells
Shyer, J. A., Flavell, R. A., & Bailis, W. (2020) · Cell Research · doi:10.1038/s41422-020-0379-5 · Cited by 346
Signaling networks in immunometabolism
Saravia, J., Raynor, J. L., Chapman, N. M., Lim, S. A., & Chi, H. (2020) · Cell Research · doi:10.1038/s41422-020-0301-1 · Cited by 258
Metadata
- Authors
- Jeng, M. Y., Hull, P. A., Fei, M., Kwon, H.-S., Tsou, C.-L., Kasler, H., Ng, C.-P., Gordon, D. E., Johnson, J., Krogan, N., Verdin, E., & Ott, M.
- Affiliations
- Gladstone Institutes (US)
- Gladstone Institutes, San Francisco, CA 1
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2017-11-30
- Volume
- 215
- Issue
- 1
- Pages
- 51-62
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC5748845
- OpenAlex
- W2771883021
- Cited by
- 121
- References
- 78
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 3 · 2023: 15 · 2022: 17 · 2021: 20 · 2020: 17 · 2019: 16 · 2018: 6 · 2017: 1
- FWCI
- 6.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (P30 AI027763, 1DP1DA038043)
- James B. Pendleton Charitable Trust (NIH S10 RR028962)
- Gladstone Institutes
- National Science Foundation (1144247)
- Evangelische Studienwerk Villigst
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
- Keywords
- CD8+CD28- T cells, SIRT1, FOXO1, metabolic reprogramming, glycolysis, memory T cells, aging, proteasomal degradation, granzyme B, cytotoxic T lymphocytes, NAD+-dependent deacetylase, transcriptional reprogramming
- MeSH terms
- Forkhead Box Protein O1, Cytotoxicity, Immunologic, Energy Metabolism, Gene Expression Regulation, Humans, Immunologic Memory, Biomarkers, T-Lymphocyte Subsets, CD28 Antigens, CD8-Positive T-Lymphocytes, Sirtuin 1
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