STAT1 drives the immune landscape of murine Toll-like receptor 9-induced liver inflammation
Our study reveals that interferon-induced STAT1 signaling is a central mediator of both systemic and hepatic inflammation during a TLR9-induced cytokine storm. Based on these findings, we support the therapeutic use of JAK1/2 inhibitors, such as ruxolitinib and baricitinib, which indirectly suppress STAT1 activity, in patients with cytokine storm syndromes and inflammatory liver disorders to alleviate both systemic and hepatic symptoms. Notably, our data also highlight the promise of direct STAT1 inhibition as a more and potentially refined approach for intervention.
Authors
- Carine Wouters
- Nele Berghmans (ORCID: https://orcid.org/0009-0003-9217-6459)
- Niels Vandamme (ORCID: https://orcid.org/0000-0001-6582-0040)
- Fran Prenen (ORCID: https://orcid.org/0000-0002-5431-1715)
- Eline Bernaerts (ORCID: https://orcid.org/0000-0002-7998-4553)
- Olivier Govaere (ORCID: https://orcid.org/0000-0002-4426-6930)
- Philippe E. Van den Steen (ORCID: https://orcid.org/0000-0002-7334-9145)
- Bert Malengier‐Devlies (ORCID: https://orcid.org/0000-0003-3527-1145)
- Patrick Matthys (ORCID: https://orcid.org/0000-0002-9685-6836)
- Jarne Beliën (ORCID: https://orcid.org/0000-0001-6731-6649)
- Hanne Meers
- Charlotte L. Scott (ORCID: https://orcid.org/0000-0003-4914-6580)
- Jochen Lamote
- Anna Bujko (ORCID: https://orcid.org/0000-0001-8693-9227)
- Tania Mitera
- Amber De Visscher (ORCID: https://orcid.org/0000-0002-9577-2390)
- Liliana Sokol (ORCID: https://orcid.org/0000-0001-9032-8971)
- Marte Vandeput (ORCID: https://orcid.org/0009-0000-0735-9612)
- Seniye Anak (ORCID: https://orcid.org/0009-0009-6440-1851)
Institutions
- Rega Institute for Medical Research (BE)
- Ghent University (BE)
- VIB-KU Leuven Center for Cancer Biology (BE)
- VIB-KU Leuven Center for Microbiology (BE)
- MRC Centre for Reproductive Health (GB)
- VIB-UGent Center for Inflammation Research (BE)
- VIB-KU Leuven Center for Brain & Disease Research (BE)
- University of Edinburgh (GB)
- KU Leuven (BE)
Publication Details
- Journal
- JHEP Reports
- Published
- 2025-11-06
- DOI
- https://doi.org/10.1016/j.jhepr.2025.101668
- Primary Topic
- Cytokine Signaling Pathways and Interactions
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fonds Wetenschappelijk Onderzoek
- KU Leuven
- Onderzoeksraad, KU Leuven
- Vlaamse regering