The β4GalT1 affects the fibroblast-like synoviocytes invasion in rheumatoid arthritis by modifying N-linked glycosylation of CXCR3

Abstract Objective The level of β-1,4-galactosyltransferase 1 (β4GalT1) is up-regulated in collagen-induced arthritis (CIA) mice. It is reported that CXC chemokine receptor 3 (CXCR3) can enhance the invasiveness of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). This study aims to investigate the specific mechanism of β4GalT1 and relationship between β4GalT1 and CXCR3 in RA. Methods The model of CIA mice was established to explore the role of β4GalT1. The N-glycosylation of CXCR3 was detected by mass spectrometry and western-blot. The interaction between β4GalT1 and CXCR3 was tested by immunoprecipitation. The truncted MMP-1 was detected by ELISA. Flow cytometry analysis was applied to measure ligand-receptor interaction between CXCR3 and CXCL10. Results β4GalT1 can promote the inflammatory process of arthritis. CXCR3 was N-glycosylated and its glycosylation regulated by β4GalT1. β4GalT1 can enhance the invasiveness of FLS by modifying CXCR3. N-glycosylation of CXCR3 influences the ligand-receptor interaction between CXCR3 and CXCL10. Conclusions β4GalT1 can regulate N-glycans of CXCR3 in RA. N-glycans of CXCR3 affects CXCL10/CXCR3 ligand-binding which enhancing FLS invasion.