2. Academic Validation
  3. Glycolytic reprogramming shapes the histone acetylation profile of activated CD4+ T cells in juvenile idiopathic arthritis

Glycolytic reprogramming shapes the histone acetylation profile of activated CD4+ T cells in juvenile idiopathic arthritis

  • Cell Rep. 2025 Feb 18;44(2):115287. doi: 10.1016/j.celrep.2025.115287.
Enric Mocholi 1,  Edward Corrigan 2,  Theo Chalkiadakis 3,  Can Gulersonmez 3,  Edwin Stigter 3,  Bas Vastert 4,  Jorg van Loosdregt 5,  Stefan Prekovic 3,  Paul J Coffer 6
Affiliations

Affiliations

  • 1 Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands; Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, the Netherlands. Electronic address: emocholi@uchceu.es.
  • 2 Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands; Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, the Netherlands.
  • 3 Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
  • 4 Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands; Division of Pediatrics, University Medical Center Utrecht, Utrecht, the Netherlands.
  • 5 Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
  • 6 Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands; Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, the Netherlands; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands. Electronic address: pcoffer@umcutrecht.nl.
PMID: 40009514 DOI: 10.1016/j.celrep.2025.115287
Abstract

Juvenile idiopathic arthritis (JIA) is an autoimmune disease characterized by accumulation of activated CD4+ T cells in the synovial fluid (SF) of affected joints. JIA CD4+ T cells exhibit a unique inflammation-associated epigenomic signature, but the underlying mechanisms remain unclear. We demonstrate that CD4+ T cells from JIA SF display heightened glycolysis upon activation and JIA-specific H3K27 acetylation, driving transcriptional reprogramming. Pharmacological inhibition of glycolysis altered the expression of genes associated with these acetylated regions. Healthy CD4+ T cells exposed to JIA SF exhibited increased glycolytic activity and transcriptomic changes marked by heightened histone 3 lysine 27 acetylation (H3K27ac) at JIA-specific genes. Elevated H3K27ac was dependent on glycolytic flux, while inhibiting glycolysis or pyruvate dehydrogenase (PDH) impaired transcription of SF-driven genes. These findings demonstrate a key role of glycolysis in JIA-specific gene expression, offering potential therapeutic targets for modulating inflammation in JIA.

Keywords

CP: Immunology; CP: Metabolism; T cells; autoimmune disease; glucose metabolism; histone acetylation; juvenile idiopathic arthritis; pyruvate dehydrogenase.

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