Oliver's mTOR Atlas Evidence Platform
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TCR-mTORC1 signaling promotes epigenetic stabilization of Foxp3 expression in regulatory T cells via TET protein translation

Kinoshita T, Hori S et al. · 2026 · Proceedings of the National Academy of Sciences of the United States of America · Atlas ID KIN2026

What this study shows

Sustained TCR signaling activates mTORC1, which boosts translation of the TET2 (and likely TET3) DNA-demethylation enzymes; this demethylates the Foxp3 TSDR enhancer and epigenetically locks in stable Foxp3 expression in regulatory T cells. In vivo mTORC1 inactivation increases methylated-TSDR Foxp3+ T cells, confirming the pathway's physiological relevance.

Abstract

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Regulatory T (Treg) cell differentiation and function rely on stable expression of the master transcription factor Foxp3. While Foxp3 expression is epigenetically stabilized through DNA demethylation of an enhancer (the Treg-specific demethylated region, TSDR), the mechanisms underlying this process remain unclear. Here, we show that strong and sustained T cell receptor (TCR) signaling promotes TSDR demethylation, stabilizes Foxp3 expression, and confers suppressive activity in in vitro-induced Treg (iTreg) cells through activation of mTORC1.

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At a glance

Evidence type M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Mouse; in vitro-induced regulatory T cells (iTreg)) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type5 - Mechanistic / In Vitro
Model systemMouse; in vitro-induced regulatory T cells (iTreg)
JournalProceedings of the National Academy of Sciences of the United States of America
Year2026
Peer reviewedYes
Record last updated2026-09-23
SourceDOI 10.1073/pnas.2612904123 · PMID 42809396

Cite this paper

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Kinoshita, T., et al. (2026). TCR-mTORC1 signaling promotes epigenetic stabilization of Foxp3 expression in regulatory T cells via TET protein translation. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.2612904123

@article{KIN2026,
  author       = {Kinoshita, T. and Hori, S. and others},
  title        = {{TCR-mTORC1 signaling promotes epigenetic stabilization of Foxp3 expression in regulatory T cells via TET protein translation}},
  journal      = {Proceedings of the National Academy of Sciences of the United States of America},
  year         = {2026},
  doi          = {10.1073/pnas.2612904123},
  note         = {PMID: 42809396},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper. 

Barton, O. (2026). Oliver's mTOR Atlas (record KIN2026) [Data set]. https://mtor-atlas.org/study/KIN2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_KIN2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record KIN2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/KIN2026/},
  doi          = {10.5281/zenodo.22059963}
}