The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Transcription Factor Foxo1 Represses T-bet-Mediated Effector Functions and Promotes Memory CD8+ T Cell Differentiation
Open accessAbstract
SUMMARY The evolutionary conserved Foxo transcription factors are important regulators of quiescence and longevity. Although, Foxo1 is known to be important in regulating CD8+ T cell trafficking and homeostasis, its role in functional differentiation of antigen stimulated CD8+ T cells is unclear. Herein, we demonstrate that inactivation of Foxo1 was essential for instructing T-bet transcription factor-mediated effector differentiation of CD8+ T cells. The Foxo1 inactivation was dependent on mTORC1 kinase, as blockade of mTORC1 abrogated mTORC2 mediated Akt (Ser473) kinase phosphorylation, resulting in Foxo1-dependent switch from T-bet to Eomesodermin transcription factor activation and increase in memory precursors. Silencing Foxo1 ablated interleukin-12 and rapamycin enhanced CD8+ T cell memory responses, and restored T-bet mediated effector functions. These results demonstrate an essential role of Foxo1 in actively repressing effector or terminal differentiation processes to promote memory CD8+ T cell development, and identify the functionally diverse mechanisms utilized by Foxo1 to promote quiescence and longevity.
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mTOR regulates memory CD8 T-cell differentiation
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Enhancing CD8 T-cell memory by modulating fatty acid metabolism
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Rao, R. R., Li, Q., Odunsi, K., & Shrikant, P. A. (2010) · Immunity · doi:10.1016/j.immuni.2009.10.010 · Cited by 656 · cited 19×
“Because inflammatory cytokines like IL-12 exert pluripotent effects on host immunity, rational strategies to regulate effector versus memory CD8+ T cell differentiation will require targeting cell-intrinsic mechanisms that regulate expression of transcriptional factors like T-bet and Eomes.”
BackgroundResultInfluentialSelf-citationFoxO transcription factors in the maintenance of cellular homeostasis during aging
Salih, D. A., & Brunet, A. (2008) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2008.02.005 · Cited by 604
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Sukumar, M., Liu, J., Ji, Y., Subramanian, M., Crompton, J. G., Yu, Z., Roychoudhuri, R., Palmer, D. C., Muranski, P., Karoly, E. D., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69589 · Cited by 952
O’Sullivan, D., van der Windt, G. J. W., Huang, S. C.-C., Curtis, J. D., Chang, C.-H., Buck, M. D., Qiu, J., Smith, A. M., Lam, W. Y., DiPlato, L. M., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.005 · Cited by 790
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Weber, E. W., Parker, K. R., Sotillo, E., Lynn, R. C., Anbunathan, H., Lattin, J., Good, Z., Belk, J. A., Daniel, B., Klysz, D., et al. (2021) · Science · doi:10.1126/science.aba1786 · Cited by 607
Metadata
- Authors
- Rao, R. R., Li, Q., Bupp, M. R. G., & Shrikant, P. A.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 36
- Issue
- 3
- Pages
- 374-387
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2080196128
- Cited by
- 293
- References
- 5
- FWCI
- 9.98
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Rao, R. R., Li, Q., Bupp, M. R. G., & Shrikant, P. A. (2012). Transcription Factor Foxo1 Represses T-bet-Mediated Effector Functions and Promotes Memory CD8+ T Cell Differentiation. Immunity. https://doi.org/10.1016/j.immuni.2012.01.015
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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