The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
T Cell Exit from Quiescence and Differentiation into Th2 Cells Depend on Raptor-mTORC1-Mediated Metabolic Reprogramming
Open accessAbstract
SUMMARY Naïve T cells respond to antigen stimulation by exiting from quiescence and initiating clonal expansion and functional differentiation, but the control mechanism is elusive. Here we describe that Raptor-mTORC1-dependent metabolic programming is a central determinant of this transitional process. Loss of Raptor abrogated T cell priming and Th2 cell differentiation, although Raptor function is less important for continuous proliferation of actively cycling cells. mTORC1 coordinated multiple metabolic programs in T cells including glycolysis, lipid synthesis and oxidative phosphorylation to mediate antigen-triggered exit from quiescence. mTORC1 further linked glucose metabolism to the initiation of Th2 cell differentiation by orchestrating cytokine receptor expression and cytokine responsiveness. Activation of Raptor-mTORC1 integrated T cell receptor and CD28 co-stimulatory signals in antigen-stimulated T cells. Our studies identify a Raptor-mTORC1-dependent pathway linking signal-dependent metabolic reprogramming to quiescence exit, and this in turn coordinates lymphocyte activation and fate decisions in adaptive immunity.
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Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
mTOR: from growth signal integration to cancer, diabetes and ageing
Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3025 · Cited by 3,941
AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849
Differentiation of Effector CD4 T Cell Populations
Zhu, J., Yamane, H., & Paul, W. E. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101212 · Cited by 3,452
The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation
Wang, R., Dillon, C. P., Shi, L. Z., Milasta, S., Carter, R., Finkelstein, D., McCormick, L. L., Fitzgerald, P., Chi, H., Munger, J., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.09.021 · Cited by 2,140 · cited 1×
“Furthermore, induction of protein but not mRNA expression of c-Myc, a crucial transcription factor for T cell glycolysis (Wang et al., 2011), was attenuated in Rptor / cells (Figures 4E and 4F).”
BackgroundSelf-citationMichalek, 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
Activation of a metabolic gene regulatory network downstream of mTOR complex 1
Düvel, K., Yecies, J. L., Menon, S., Raman, P., Lipovsky, A. I., Souza, A. L., Triantafellow, E., Ma, Q., Gorski, R., Cleaver, S., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.06.022 · Cited by 2,020
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Self-citationmTOR regulates memory CD8 T-cell differentiation
Araki, K., Turner, A. P., Shaffer, V. O., Gangappa, S., Keller, S. A., Bachmann, M. F., Larsen, C. P., & Ahmed, R. (2009) · Nature · doi:10.1038/nature08155 · Cited by 1,575
The CD28 Signaling Pathway Regulates Glucose Metabolism
Frauwirth, K. A., Riley, J. L., Harris, M. H., Parry, R. V., Rathmell, J. C., Plas, D. R., Elstrom, R. L., June, C. H., & Thompson, C. B. (2002) · Immunity · doi:10.1016/s1074-7613(02)00323-0 · Cited by 1,475 · cited 1×
“In contrast, CD28 costimulation markedly potentiated glycolysis (Frauwirth et al., 2002) (Figure 7A) and also enhanced T cell growth, upregulation of nutrient receptors, and lipid synthesis in TCR-stimulated cells (Figure S7A).”
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Cited by
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Gieseck, R. L., Wilson, M. S., & Wynn, T. A. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.90 · Cited by 1,055
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Ganeshan, K., & Chawla, A. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120236 · Cited by 926
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Walker, J. A., & McKenzie, A. N. J. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.118 · Cited by 632
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Wei, J., Long, L., Yang, K., Guy, C., Shrestha, S., Chen, Z., Wu, C., Vogel, P., Neale, G., Green, D. R., et al. (2016) · Nature Immunology · doi:10.1038/ni.3365 · Cited by 470
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Metadata
- Authors
- Yang, K., Shrestha, S., Zeng, H., Karmaus, P. W. F., Neale, G., Vogel, P., Guertin, D. A., Lamb, R. F., & Chi, H.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 39
- Issue
- 6
- Pages
- 1043-1056
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2084561923
- Cited by
- 394
- References
- 15
- FWCI
- 12.74
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Yang, K., Shrestha, S., Zeng, H., Karmaus, P. W. F., Neale, G., Vogel, P., Guertin, D. A., Lamb, R. F., & Chi, H. (2013). T Cell Exit from Quiescence and Differentiation into Th2 Cells Depend on Raptor-mTORC1-Mediated Metabolic Reprogramming. Immunity. https://doi.org/10.1016/j.immuni.2013.09.015
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