Tyro3 receptor tyrosine kinase contributes to pathogenic phenotypes of fibroblast-like synoviocytes in rheumatoid arthritis and disturbs immune cell balance in experimental arthritis.

Ziye Wang, Zhen Zhao, Zhichang Li, Liling Xu, Hongchao Li, Huaqun Zhu, Gong Cheng, RanRan Yao, Wenwen Pei, Ruyu Liang, Renge Liang, Hua Ye, Shan Jiang, Haitao Niu, Xiaolin Sun, Yin Su

Clinical immunology (Orlando, Fla.) 2023 Oct

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Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by synovitis and joint damage, the underlying causes of which remain unclear. Our prior investigations revealed a notable correlation between the expression of Tyro3 Protein Tyrosine Kinase (Tyro3TK) and the progression of RA. To further elucidate the pathogenic role of Tyro3TK in RA, we analyzed the influence of Tyro3TK on pathogenic phenotypes of RA fibroblast like synoviocyte (FLS) in vitro and compared disease severity, joint damages and immunological parameters of K/BxN serum transfer arthritis (STA) in Tyro3TK-/- deficient mice and wild type controls. Our findings underscored the remarkable effectiveness of Tyro3TK blockade, as evidenced by diminished secretion of inflammatory cytokines and matrix metalloproteinases (MMPs), curtailed migration and invasiveness of RAFLS, and attenuated differentiation of pathogenic helper T cell subsets mediated by RAFLS. Correspondingly, our in vivo investigations illuminated the more favorable outcomes in Tyro3TK-deficient mice, characterized by reduced joint pathology, tempered synovial inflammation, and restored immune cell equilibrium. These data suggested that Tyro3TK might contribute to aggravated autoimmune arthritis and immunological pathology and act as a potential therapeutic target for RA. Copyright © 2023 Elsevier Inc. All rights reserved.

Citation

Ziye Wang, Zhen Zhao, Zhichang Li, Liling Xu, Hongchao Li, Huaqun Zhu, Gong Cheng, RanRan Yao, Wenwen Pei, Ruyu Liang, Renge Liang, Hua Ye, Shan Jiang, Haitao Niu, Xiaolin Sun, Yin Su. Tyro3 receptor tyrosine kinase contributes to pathogenic phenotypes of fibroblast-like synoviocytes in rheumatoid arthritis and disturbs immune cell balance in experimental arthritis. Clinical immunology (Orlando, Fla.). 2023 Oct;255:109753