Lysozyme modulates inflammatory responses to exacerbate the severity of rheumatoid arthritis

The mechanisms underlying Rheumatoid Arthritis (RA) remain unclear. Despite having relatively well-defined treatment strategies, current therapeutic approaches only achieve a remission rate of 70 %–80 %, with poor prognosis and no clear diagnostic criteria for early RA. Therefore, there is a need for new therapeutic targets or biomarkers to improve the treatment of RA. Firstly, we identified the expression characteristics of lysozyme (LYZ) in early RA patients through plasma proteomics and synovial fluid single-cell sequencing analysis. Secondly, we constructed Lyz1 cKO mice to investigate the role of Lyz1 in RA pathogenesis using the Collagen Antibody-Induced Arthritis (CAIA) mouse model. Thirdly, we silenced LYZ to clarify its impact on TNF-α-induced inflammatory cytokine release and other inflammatory phenotypes in MH7A cells. Finally, we explored the cellular pathways involving LYZ in fibroblast-like synoviocytes (FLSs) and changes in RA-related genes through RNA sequencing (RNA-Seq). LYZ was highly expressed in the plasma and synovial macrophages of early RA patients. The absence of Lyz1 reduced the arthritis course and joint damage in CAIA mice. Silencing LYZ promoted the proliferation and apoptosis of MH7A cells and improved their inflammatory phenotypes, possibly through the regulation of the TNF signaling pathway. LYZ is highly expressed in the plasma and synovial fluid macrophages of early RA patients and exacerbates RA progression by modulating inflammation-related pathways, demonstrating potential as a biomarker for early RA diagnosis or a therapeutic target. Lysozyme modulates inflammatory responses to exacerbate the severity of rheumatoid arthritis. • Lysozyme (LYZ) is overexpressed in the plasma of RA early patients. • LYZ is highly expressed in synovial fluid macrophages of early RA patients. • Lyz1-deficient mice exhibit reduced severity of arthritis. • Silencing of LYZ ameliorates the inflammatory phenotype of MH7A cells. • LYZ shows potential as a diagnostic biomarker or molecular target for early RA.