PhD Scientific Days 2026

Poster Session 2.B - Molecular Medicine

The Effect of Synovial Fibroblast-specific Syk Deletion in a Chronic Polyarthritis Model in Mice

Name of the presenter

Majerhoffer, Nóra

Institute/workplace of the presenter

Department of Physiology, Semmelweis University

Authors

Nóra Majerhoffer^1,2, Alexander S. Boone^1,2, Adrienn Bóka^1,2, Attila Mócsai¹, Tamás Németh^1,2,3
1: Department of Physiology, Semmelweis University, Budapest, Hungary
2: MTA-SE “Lendület” Translational Rheumatology Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary
3: Department of Rheumatology and Immunology, Semmelweis University, Budapest, Hungary

Text of the abstract

Introduction: Rheumatoid arthritis causes synovitis and joint destruction, which is partly mediated by synovial fibroblasts (FLS). Since many patients do not respond to current available therapies, novel therapeutic targets and drugs must be identified. Syk is an intracellular tyrosine-kinase that is present in synovial fibroblasts, has been shown to contribute to the development of experimental autoimmune arthritis, while its expression is upregulated in the rheumatoid arthritis synovium.
Aims: Here, we investigated the role of the Syk tyrosine-kinase in synovial fibroblasts in the development of a chronic experimental arthritis.
Methods: FLS-specific deletion of Syk was achieved by the Cre-Lox system (resulting in SykΔFLS mice). We induced chronic polyarthritis by ovalbumin-specific T cell injection and repeated ovalbumin exposure in wild type and SykΔFLS mice. Arthritis was followed by ankle thickness measurement, clinical scoring and a functional test. Pannus formation was examined by histological analysis, while local immune cell accumulation was measured by flow cytometry. Proinflammatory cytokine levels and autoantibody titers were detected by ELISA. The presence of bone erosions was examined by micro-CT analysis.
Results: SykΔFLS mice developed milder joint inflammation compared to the wild type animals. In line with these findings, pannus formation was less severe, immune cell accumulation and proinflammatory cytokine levels were also lower in SykΔFLS mice. Moreover, FLS-specific Syk expression was critical for the development of bone erosions and autoantibody production.
Conclusions: Our results indicate that Syk expression in synovial fibroblasts is important for the development of experimental chronic arthritis. These data propose that Syk inhibition may have a beneficial effect in the treatment of human autoimmune arthritis.
Funding: This work was funded by the Hungarian National Research, Development and Innovation Office and the Lendület program of the Hungarian Academy of Sciences. Nóra Majerhoffer is a recipient of an SE 250+ Excellence PhD Scholarship.