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

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.