The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
The Glucose Transporter Glut1 Is Selectively Essential for CD4 T Cell Activation and Effector Function
Open accessAbstract
SUMMARY CD4 T cell activation leads to rapid proliferation and differentiation into effector (Teff) or regulatory (Treg) cells that mediate or control immunity. While Teff and Treg prefer distinct glycolytic or oxidative metabolic programs in vitro, requirements and mechanisms that control T cell glucose uptake and metabolism in vivo are poorly understood. Despite expression of multiple glucose transporters, Glut1-deficiency selectively impaired metabolism and function of thymocytes and Teff. Resting T cells were normal until activated, when Glut1-deficiency prevented increased glucose uptake and glycolysis, growth, proliferation, and decreased cell survival and Teff differentiation. Importantly, Glut1-deficiency decreased Teff expansion and ability to induce inflammatory disease in vivo. Treg, in contrast, were enriched in vivo and appeared functionally unaffected by Glut1-deficiency and able to suppress Teff irrespective of Glut1 expression. These data show a selective in vivo requirement for Glut1 in metabolic reprogramming of CD4 T cell activation and Teff expansion and survival.
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Cites
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
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Differentiation of Effector CD4 T Cell Populations
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The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation
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“In addition to the cMyc (Wang et al., 2011) and estrogenrelated receptor a (ERRa) (Michalek et al., 2011b) transcription factors that regulate T cell metabolism, mTOR and the PI3KAkt-mTORC1 signaling pathway can promote Glut1 cell-surface trafficking, glycolysis, and lipid synthesis (Düvel et al.,…”
InfluentialMichalek, R. D., Gerriets, V. A., Jacobs, S. R., Macintyre, A. N., MacIver, N. J., Mason, E. F., Sullivan, S. A., Nichols, A. G., & Rathmell, J. C. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003613 · Cited by 2,091
Self-citationActivation of a metabolic gene regulatory network downstream of mTOR complex 1
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The CD28 Signaling Pathway Regulates Glucose Metabolism
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“In vitro-stimulated murine and human T cells express high levels of Glut1 (Slc2a1) (Frauwirth et al., 2002; Jacobs et al., 2008), and Teff cells maintain levels of Glut1 higher than those of Treg (Michalek et al., 2011a).”
InfluentialSelf-citationMetabolic Regulation of T Lymphocytes
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Self-citationMetabolic support of tumour-infiltrating regulatory T cells by lactic acid
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Foxp3 Reprograms T Cell Metabolism to Function in Low-Glucose, High-Lactate Environments
Angelin, A., Gil-de-Gómez, L., Dahiya, S., Jiao, J., Guo, L., Levine, M. H., Wang, Z., Quinn, W. J., Kopinski, P. K., Wang, L., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.12.018 · Cited by 1,246
Lactate: the ugly duckling of energy metabolism
Rabinowitz, J. D., & Enerbäck, S. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0243-4 · Cited by 1,049
Glucose Metabolism Regulates T Cell Activation, Differentiation, and Functions
Palmer, C. S., Ostrowski, M., Balderson, B., Christian, N., & Crowe, S. M. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00001 · Cited by 988
Metadata
- Authors
- Macintyre, A. N., Gerriets, V. A., Nichols, A. G., Michalek, R. D., Rudolph, M. C., Deoliveira, D., Anderson, S. M., Abel, E. D., Chen, B. J., Hale, L. P., & Rathmell, J. C.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 20
- Issue
- 1
- Pages
- 61-72
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W1992250154
- Cited by
- 1,127
- References
- 16
- FWCI
- 26.32
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Macintyre, A. N., Gerriets, V. A., Nichols, A. G., Michalek, R. D., Rudolph, M. C., Deoliveira, D., Anderson, S. M., Abel, E. D., Chen, B. J., Hale, L. P., & Rathmell, J. C. (2014). The Glucose Transporter Glut1 Is Selectively Essential for CD4 T Cell Activation and Effector Function. Cell Metabolism. https://doi.org/10.1016/j.cmet.2014.05.004
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