From model to man: Understanding Tregs' dual role in MASLD
Diet-induced steatohepatitis can develop without adaptive immunity, yet IL-17A-expressing Foxp3<sup>+</sup> T regulatory cells (Tregs) and CD8<sup>+</sup> T cells markedly amplify hepatocellular injury and fibrosis. By separating initiating (macrophage-driven) from amplifying (adaptive) immune signals, our study refines current pathogenic models and provides hepatologists and immunologists with stage-specific therapeutic targets. For clinicians and trial designers, the data indicate that stabilizing Tregs or selectively dampening pro-inflammatory T-cell subsets could complement metabolic interventions in metabolic dysfunction-associated steatotic liver disease/steatohepatitis, whereas indiscriminate Treg expansion might be counter-productive. Because the conclusions are drawn from a murine model, translation to humans will require validation in patient-derived tissues and non-invasive immune biomarkers.
Authors
- Michael P. Manns (ORCID: https://orcid.org/0000-0002-4485-8856)
- Ana Clara Marques Davalos‐Misslitz
- Janine Dywicki
- Christian Koenecke (ORCID: https://orcid.org/0000-0001-7025-1735)
- Richard Taubert (ORCID: https://orcid.org/0000-0001-9270-2496)
- Elmar Jaeckel (ORCID: https://orcid.org/0000-0003-4108-7192)
- Christine S. Falk (ORCID: https://orcid.org/0000-0003-1376-7318)
- Katharina Luise Hupa‐Breier (ORCID: https://orcid.org/0000-0002-8372-616X)
- Benjamin Heidrich (ORCID: https://orcid.org/0000-0002-0213-3873)
- Jérôme Schlué
- Maren Lieber
- Celina M. Hendriks
- Laura Elisa Buitrago‐Molina (ORCID: https://orcid.org/0000-0002-0051-2044)
- Freya Wellhöner (ORCID: https://orcid.org/0000-0002-9031-2731)
- Matthias Blüher (ORCID: https://orcid.org/0000-0003-0208-2065)
- Fatih Noyan (ORCID: https://orcid.org/0000-0001-6250-8692)
- Heiner H. Wedemeyer (ORCID: https://orcid.org/0000-0003-2906-0480)
- Matthias Hardtke‐Wolenski (ORCID: https://orcid.org/0000-0002-2827-7787)
- Anna Baumann (ORCID: https://orcid.org/0000-0003-2086-0334)
- Heike Bantel
Institutions
- University Health Network (CA)
- Leipzig University of Applied Sciences (DE)
- Medizinische Hochschule Hannover (DE)
- Essen University Hospital (DE)
- University Hospital Leipzig (DE)
- IFB Adiposity Diseases (DE)
- University of Duisburg-Essen (DE)
- Leipzig University (DE)
Publication Details
- Journal
- JHEP Reports
- Published
- 2025-10-09
- DOI
- https://doi.org/10.1016/j.jhepr.2025.101619
- Citations
- 2
- Primary Topic
- Genetic Syndromes and Imprinting
- Type
- article
- Field-Weighted Citation Impact
- 3.63