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Functional reprogramming of regulatory T cells in the absence of Foxp3
Open accessAbstract
Regulatory T cells (T reg cells) deficient in the transcription factor Foxp3 lack suppressor function and manifest an effector T (T eff) cell-like phenotype. We demonstrate that Foxp3 deficiency dysregulates metabolic checkpoint kinase mammalian target of rapamycin (mTOR) complex 2 (mTORC2) signaling and gives rise to augmented aerobic glycolysis and oxidative phosphorylation. Specific deletion of the mTORC2 adaptor gene Rictor in Foxp3-deficient T reg cells ameliorated disease in a Foxo1 transcription factor-dependent manner. Rictor deficiency re-established a subset of T reg cell genetic circuits and suppressed the T eff cell-like glycolytic and respiratory programs, which contributed to immune dysregulation. Treatment of T reg cells from patients with FOXP3 deficiency with mTOR inhibitors similarly antagonized their T eff cell-like program and restored suppressive function. Thus, regulatory function can be re-established in Foxp3-deficient T reg cells by targeting their metabolic pathways, providing opportunities to restore tolerance in T reg cell disorders.
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“AKT/mTOR/HIF1α signaling has been suggested to play critical roles in promoting glycolysis and lactate production and thus in the “metabolic reprogramming” of cancer cells24–28.”
From RETRACTED ARTICLE: Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression (2020) · cites this paper as [26]
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Cites
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216
AKT/PKB Signaling: Navigating the Network
Manning, B. D., & Toker, A. (2017) · Cell · doi:10.1016/j.cell.2017.04.001 · Cited by 3,772
Regulatory T cells: mechanisms of differentiation and function
Josefowicz, S. Z., Lu, L.-F., & Rudensky, A. Y. (2012) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141623 · Cited by 2,866
CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells
Liu, W., Putnam, A. L., Xu-yu, Z., Szot, G. L., Lee, M. R., Zhu, S., Gottlieb, P. A., Kapranov, P., Gingeras, T. R., de St. Groth, B. F., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060772 · Cited by 2,606
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
Michalek, 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
Shi, L. Z., Wang, R., Huang, G., Vogel, P., Neale, G., Green, D. R., & Chi, H. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20110278 · Cited by 1,803
Transcriptional control of effector and memory CD8+ T cell differentiation
Kaech, S. M., & Cui, W. (2012) · Nature Reviews Immunology · doi:10.1038/nri3307 · Cited by 1,628
Role of PFKFB3-Driven Glycolysis in Vessel Sprouting
Bock, K. D., Γεωργιάδου, Μ., Schoors, S., Kuchnio, A., Wong, B. W., Cantelmo, A. R., Quaegebeur, A., Ghesquière, B., Cauwenberghs, S., Eelen, G., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.037 · Cited by 1,591
Self-citationSeddiki, N., Santner-Nanan, B., Martinson, J., Zaunders, J., Sasson, S., Landay, A., Solomon, M., Selby, W., Alexander, S. I., Nanan, R., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060468 · Cited by 1,512
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Zafar, M. A., Machado, C. N. H., Behera, J., Zhong, Y., Li, X., Joshi, S., Fazaa, Y. E., Camacho, V., Georgiev, P., Haigis, M. C., et al. (2026) · The Journal of Immunology · doi:10.1093/jimmun/vkag141.680
Self-citationRayes, A., Ramachandran, A., Pulsipher, M. A., Dolan, J. G., Cho, S., Johnson, A. K., Alexander, J. L. A., Borna, Š., & Bacchetta, R. (2026) · Journal of Human Immunity · doi:10.70962/jhi.20250249
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Yuan, M., Sun, T., Qiao, Y., Muro, P., Wang, B., Zhou, X., & Mao, F. (2026) · Stem Cells International · doi:10.1155/sci/6457805
Lien, C., Chang, H.-Y., Yu, S.-H., Cho, R., Chen, S., Kuo, T.-T., Chong, P. C. T., Ye, C.-H., Lin, F., Wu, W.-L., et al. (2026) · Experimental & Molecular Medicine · doi:10.1038/s12276-026-01842-9
Kinoshita, T., Nakajima, A., Kobayashi, T., Ohno, M., wei, Y., Hasegawa, T., Hayatsu, N., Hirayama, S., Tsukada, Y.-I., Hirao, A., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2612904123
Mishra, S. K., Abdelrahman, L. M., Lee, H. S. K., Valenzuela-Pérez, L., Manna, D. F., Abram, T. J., Ali, L. M., Davidson, H. M., Hassan, O. M., Faubion, W. A., et al. (2026) · Science Signaling · doi:10.1126/scisignal.aeb2392
Krol, A. L., Silva, L., Nascimento, D. C., Oberwalder, S. M., Chawla, H., de Carvalho, G. A. B., Boukhallouk, F., Romero, M., Hausen, A., Gaida, M. M., et al. (2026) · European Journal of Immunology · doi:10.1002/eji.70297
Metadata
- Authors
- Charbonnier, L.-M., Cui, Y., Stephen-Victor, E., Harb, H., Lopez, D., Bleesing, J. J., Garcia-Lloret, M. I., Chen, K., Ozen, A., Carmeliet, P., Li, M. O., Pellegrini, M., & Chatila, T. A.
- Affiliations
- Boston Children's Hospital (US)
- University of California, Los Angeles (US)
- Cincinnati Children's Hospital Medical Center (US)
- University of Utah (US)
- Marmara University (TR)
- VIB-KU Leuven Center for Cancer Biology (BE)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Chatila, Talal A.
- ORCID
- Venue
- Nature Immunology
- Published
- 2019-08-05
- Volume
- 20
- Issue
- 9
- Pages
- 1208-1219
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC6707855
- OpenAlex
- W2966678440
- Cited by
- 145
- References
- 55
- Citations by year
- 2026: 14 · 2025: 12 · 2024: 14 · 2023: 16 · 2022: 26 · 2021: 24 · 2020: 32 · 2019: 7
- FWCI
- 8.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Dspace Repository (Marmara Üniversitesi) (submittedVersion, other-oa)
- Lirias (KU Leuven) (submittedVersion)
- Dspace Repository (Marmara Üniversitesi) (submittedVersion)
- Funders
- National Institutes of Health (5r01ai085090-10)
- National Cancer Institute (P30CA008748, P30CA016042)
- National Institute of Allergy and Infectious Diseases (R01-AI-085090, R01AI102888, R01AI065617)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK034854)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Keywords
- regulatory T cells, mTORC2 signaling, Rictor, aerobic glycolysis, oxidative phosphorylation, FOXO1, mTOR inhibitors, immune tolerance, immune dysregulation
- MeSH terms
- Mechanistic Target of Rapamycin Complex 2, Rapamycin-Insensitive Companion of mTOR Protein, Animals, Cells, Cultured, Female, Gene Expression Regulation, Glycolysis, Humans, Male, Mice, Inbred C57BL, Oxidative Phosphorylation, Signal Transduction, Mice, Knockout, T-Lymphocytes, Regulatory, Mice, Forkhead Transcription Factors, Cellular Reprogramming
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