Stueve, Philipp and Godoy, Gloria J. and Ferreyra, Fernando N. and Hellriegel, Florencia and Boukhallouk, Fatima and Kao, Yu-San and More, Tushar H. and Matthies, Anne-Marie and Akimova, Tatiana and Abraham, Wolf-Rainer and Kaever, Volkhard and Schmitz, Ingo and Hiller, Karsten and Lochner, Matthias and Salomon, Benoit L. and Beier, Ulf H. and Rehli, Michael and Sparwasser, Tim and Berod, Luciana (2025) ACC1 is a dual metabolic-epigenetic regulator of Treg stability and immune tolerance. MOLECULAR METABOLISM, 94: 102111. ISSN 2212-8778,
Full text not available from this repository. (Request a copy)Abstract
Objective: Regulatory T cells (Tregs) are essential in maintaining immune tolerance and controlling inflammation. Treg stability relies on transcriptional and post-translational mechanisms, including histone acetylation at the Foxp3 locus and FoxP3 protein acetylation. Additionally, Tregs depend on specific metabolic programs for differentiation, yet the underlying molecular mechanisms remain elusive. We aimed to investigate the role of acetyl-CoA carboxylase 1 (ACC1) in the differentiation, stability, and function of regulatory T cells (Tregs). Methods: We used either T cell-specific ACC1 knockout mice or ACC1 inhibition via a pharmacological agent to examine the effects on Treg differentiation and stability. The impact of ACC1 inhibition on Treg function was assessed in vivo through adoptive transfer models of Th1/Th17driven inflammatory diseases. Results: Inhibition or genetic deletion of ACC1 led to an increase in acetyl-CoA availability, promoting enhanced histone and protein acetylation, and sustained FoxP3 transcription even under inflammatory conditions. Mice with T cell-specific ACC1 deletion exhibited an enrichment of double positive RORgt+FoxP3+ cells. Moreover, Tregs treated with an ACC1 inhibitor demonstrated superior long-term stability and an enhanced capacity to suppress Th1/Th17-driven inflammatory diseases in adoptive transfer models. Conclusions: We identified ACC1 as a metabolic checkpoint in Treg biology. Our data demonstrate that ACC1 inhibition promotes Treg differentiation and long-term stability in vitro and in vivo. Thus, ACC1 serves as a dual metabolic and epigenetic hub, regulating immune tolerance and inflammation by balancing de novo lipid synthesis and protein acetylation. (c) 2025 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACETYL-COA CARBOXYLASE; FATTY-ACID SYNTHESIS; T-CELLS; DNA METHYLATION; FOXP3 GENE; PROINFLAMMATORY IL-17(+); TGF-BETA; IN-VIVO; INHIBITION; DIFFERENTIATION; ACC1; Adoptive Treg transfer; Epigenetic regulation; Fatty acid synthesis; Treg stability; Acetylation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Apr 2026 09:24 |
| Last Modified: | 01 Apr 2026 09:24 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67753 |
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