DNA (cytosine-5)-methyltransferase 3A (Dnmt3a) mutations limit normal and autoreactive CD4+ T follicular helper responses and attenuate T cell-driven joint inflammation - Report - MDSpire

Mutations in DNA (cytosine-5)-methyltransferase 3A (Dnmt3a) impair both typical and autoreactive CD4+ T follicular helper cell functions and reduce T cell-mediated joint inflammation

  • By

  • Yunbing Shen

  • Sanjaykumar Boddul

  • Zhaojun Li

  • Zsolt Kasza

  • Marlene Schülein

  • Bruno Raposo

  • Karine Chemin

  • Per-Johan Jakobsson

  • Alexander Espinosa

  • Lars Klareskog

  • Fredrik Wermeling

  • June 29, 2026

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Mutations in Dnmt3a Impair CD4+ T Follicular Helper Cell Functions

Overview

This study investigates the impact of Dnmt3a mutations on CD4+ T follicular helper (Tfh) cell functions and T cell-mediated joint inflammation.

Background

Understanding the role of Dnmt3a mutations is crucial as they are linked to various autoimmune conditions, including rheumatoid arthritis (RA). CD4+ Tfh cells are essential for B cell help and autoantibody production.

Data Highlights

No numerical data or trial data were provided in the source material.

Key Findings

  • Dnmt3a mutations impair normal CD4+ Tfh cell functions.
  • Autoreactive CD4+ Tfh responses are also significantly affected by these mutations.
  • Reduced T cell-mediated joint inflammation was observed in models with Dnmt3a mutations.

Clinical Implications

Clinicians should consider the potential impact of Dnmt3a mutations on Tfh cell function when evaluating patients with autoimmune conditions. Understanding these mechanisms may aid in the development of targeted therapies for conditions like rheumatoid arthritis.

Conclusion

The study underscores the critical role of Dnmt3a in regulating Tfh cell functions and its implications for T cell-mediated inflammation in autoimmune diseases.

Related Resources & Content

  1. Yunbing Shen et al., PubMed, 2023 -- Mutations in DNA (cytosine-5)-methyltransferase 3A (Dnmt3a) impair both typical and autoreactive CD4+ T follicular helper cell functions and reduce T cell-mediated joint inflammation
  2. Blood Cancer Journal — Reduced TET2 function leads to T-cell lymphoma with follicular helper T-cell-like features in mice
  3. Blood Cancer Journal — High DNA-methyltransferase 3B expression predicts poor outcome in acute myeloid leukemia, especially among patients with co-occurring NPM1 and FLT3 mutations
  4. Blood Cancer Journal — Uncommon DNMT3A Mutations in Myeloproliferative Neoplasms and Myelodysplastic Syndromes
  5. Blood Cancer Journal — Upregulation of TET activity with ascorbic acid induces epigenetic modulation of lymphoma cells
  6. EULAR 2025 Update on Rheumatoid Arthritis DMARD Management
  7. DNA (cytosine-5)-methyltransferase 3A (Dnmt3a) mutations limit normal and autoreactive CD4+ T follicular helper responses and attenuate T cell-driven joint inflammation - PubMed
  8. Vagus nerve-mediated neuroimmune modulation for rheumatoid arthritis: a pivotal randomized controlled trial | Nature Medicine

Original Source(s)

DNA (cytosine-5)-methyltransferase 3A (Dnmt3a) mutations limit normal and autoreactive CD4+ T follicular helper responses and attenuate T cell-driven joint inflammation

  • by Yunbing Shen, Sanjaykumar Boddul, Zhaojun Li, Zsolt Kasza, Marlene Schülein, Bruno Raposo, Karine Chemin, Per-Johan Jakobsson, Alexander Espinosa, Lars Klareskog, Fredrik Wermeling

  • June 29, 2026

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