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Distinct strengths of mTORC1 control T-cell memory via transcriptional FOXO1 and metabolic AMPKα1 pathways in linear cell differentiation and asymmetric cell division models

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References

  1. Chen Y, Zander R, Khatun A, Schauder DM, Cui W. Transcriptional and epigenetic regulation of effector and memory CD8 T cell differentiation. Front Immunol. 2018;9:2826 https://doi.org/10.3389/fimmu.2018.02826

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. Lanzavecchia A, Sallusto F. Dynamics of T lymphocyte responses: intermediates, effectors, and memory cells. Science. 2000;290:92–7. https://doi.org/10.1126/science.290.5489.92

    CAS  Article  PubMed  Google Scholar 

  3. Chang JT, Palanivel VR, Kinjyo I, Schambach F, Intlekofer AM, Banerjee A, et al. Asymmetric T lymphocyte division in the initiation of adaptive immune responses. Science. 2007;315:1687–91. https://doi.org/10.1126/science.1139393

    CAS  Article  PubMed  Google Scholar 

  4. Daniels MA, Teixeiro E. TCR signaling in T cell memory. Front Immunol. 2015;6:617 https://doi.org/10.3389/fimmu.2015.00617

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. Kalia V, Sarkar S. Regulation of effector and memory CD8 T cell differentiation by IL-2-A balancing act. Front Immunol. 2018;9:2987 https://doi.org/10.3389/fimmu.2018.02987

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. Jung J, Zeng H, Horng T. Metabolism as a guiding force for immunity. Nat Cell Biol. 2019;21:85–93. https://doi.org/10.1038/s41556-018-0217-x

    CAS  Article  PubMed  Google Scholar 

  7. Araki K, Turner AP, Shaffer VO, Gangappa S, Keller SA, Bachmann MF, et al. mTOR regulates memory CD8 T-cell differentiation. Nature. 2009;460:108–12. https://doi.org/10.1038/nature08155

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Rao RR, Li Q, Gubbels Bupp MR, Shrikant PA. Transcription factor Foxo1 represses T-bet-mediated effector functions and promotes memory CD8(+) T cell differentiation. Immunity. 2012;36:374–87. https://doi.org/10.1016/j.immuni.2012.01.015

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. Cieri N, Camisa B, Cocchiarella F, Forcato M, Oliveira G, Provasi E, et al. IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors. Blood. 2013;121:573–84. https://doi.org/10.1182/blood-2012-05-431718

    CAS  Article  PubMed  Google Scholar 

  10. Xu A, Leary SC, Islam MF, Wu Z, Bhanumathy KK, Ara A, et al. Prosurvival IL-7-stimulated weak strength of mTORC1-S6K controls T cell memory via transcriptional FOXO1-TCF1-Id3 and metabolic AMPKα1-ULK1-ATG7 Pathways. J Immunol. 2022;208:155–68. https://doi.org/10.4049/jimmunol.2100452

    CAS  Article  PubMed  Google Scholar 

  11. Ara A, Xu A, Ahmed KA, Leary SC, Islam MF, Wu Z, et al. The energy sensor AMPKα1 is critical in rapamycin-inhibition of mTORC1-S6K-induced T-cell memory. Int J Mol Sci. 2022;23:37 https://doi.org/10.3390/ijms23010037

    CAS  Article  Google Scholar 

  12. King CG, Koehle S, Hausmann B, Schmaler M, Zehn D, Palmer E. T cell affinity regulates asymmetric division, effector cell differentiation, and tissue pathology. Immunity. 2012;37:709–20. https://doi.org/10.1016/j.immuni.2012.06.021

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Arsenio J, Kakaradov B, Metz PJ, Kim SH, Yeo GW, Chang JT. Early specification of CD8+ T lymphocyte fates during adaptive immunity revealed by single-cell gene-expression analyses. Nat Immunol. 2014;15:365–72. https://doi.org/10.1038/ni.2842

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. Verbist KC, Guy CS, Milasta S, Liedmann S, Kamiński MM, Wang R, et al. Metabolic maintenance of cell asymmetry following division in activated T lymphocytes. Nature. 2016;532:389–93. https://doi.org/10.1038/nature17442

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Pollizzi KN, Sun IH, Patel CH, Lo YC, Oh MH, Waickman AT, et al. Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8(+) T cell differentiation. Nat Immunol. 2016;17:704–11. https://doi.org/10.1038/ni.3438

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by a research grant (#PJT153314) from the Canadian Institute of Health Research (CIHR).

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Correspondence to Jim Xiang.

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Huang, J., Leary, S. & Xiang, J. Distinct strengths of mTORC1 control T-cell memory via transcriptional FOXO1 and metabolic AMPKα1 pathways in linear cell differentiation and asymmetric cell division models. Cell Mol Immunol 19, 1073–1076 (2022). https://doi.org/10.1038/s41423-022-00879-w

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