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July 30, 2026The Journal of Immunology

Loss of TET function in T regulatory cells yields Tfh-like ex-Treg cells with the features of heterochromatin dysfunction 2266533

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Authors

KSKazumasa SuzukiLa Jolla Institute for ImmunologyLALeo Arteaga-VazquezLa Jolla Institute for ImmunologyBRBruno Villalobos RevelesLa Jolla Institute for Immunology

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Implication

Randomized trial reveals that loss of TET function in T regulatory cells induces inflammation in a model organism, indicating altered immune dynamics.

Key Points

  • This research examines how the loss of TET function in T regulatory cells leads to the conversion into pathogenic Tfh-like ex-Treg cells.
  • CD4+ FOXP3+ Tregs from WT or CD4-Cre Tet2/3fl/fl mice were co-transferred with naïve CD4+ T cells into Rag1⁻/⁻ mice.
  • RNA sequencing was utilized to analyze gene expression profiles of Tregs and ex-Tregs.
  • ChIP-seq was performed to study FOXP3 binding and its regulatory effects on transposable elements.
  • Tet2/3 double-knockout Tregs lost FOXP3 and CD4 expression, generating FOXP3⁻ CD4⁻ ex-Treg cells.
  • Tet2/3 DKO ex-Tregs expressed Tfh-related genes and induced severe inflammation upon transfer, leading to expansion of plasma cells and CD8+ T cells.
  • Hypermethylation at Prdm1 and Bcl6 loci was observed, with FOXP3 potentially regulating transposable element expression.

Cite This Study

Suzuki et al. (2026) studied this question.

synapsesocial.com/papers/6a6af54a60e2b924d3ea151bhttps://doi.org/10.1093/jimmun/vkag141.1096
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Loss of TET function in T regulatory cells yields ex-Treg cells biased toward T follicular helper cells, causing autoimmune diseases through autoantibody production2025 · 1 citations
  2. 2Loss of TET function in T regulatory cells yields ex-Treg cells biased toward T follicular helper cells, causing autoimmune diseases through autoantibody production2026 · 5 citations
  3. 3Assessing the impact of TET2 and TET3 deletion in TCRalpha and TCRbeta repertoire in murine CD4 T cells in physiological and pathophysiological conditions2025 · 3 citations
  4. 4Tet2 deficiency alters CD4+ T cell function and promotes T cell lymphoma with a TFH cell immunophenotype2026
  5. 5Defects in CD8+ T cell suppression by Foxp3-dE2 regulatory T cells 22577492026