Lysozyme modulates inflammatory responses to exacerbate the severity of rheumatoid arthritis

IF 4.8 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-03-08 DOI:10.1016/j.intimp.2025.114427

Hao Xu , Luxu Yin , Liang Zou , Enshui Zhang , Yang Cheng , Wenyue Zhang , Yihong Liu , Jinxiang Han , Yan Zhao

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引用次数: 0

Abstract

Background

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.

Methods

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).

Results

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.

Conclusion

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.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.