Low dose methotrexate impaired T cell transmigration through down-regulating CXCR4 expression in rheumatoid arthritis (RA)
Authors' conclusion
Our findings suggest that the effect of low dose MTX treatment could serve to eliminate inflammation in RA patients through impairment of immune cell transmigration mediated by CXCR4.
Study context
- Population
- Peripheral T cells from RA patients and arthritis mice models receiving low dose methotrexate (MTX)
- Comparison
- Low dose MTX vs no MTX; Cxcr4 conditional knockout (CKO) vs non-CKO arthritis mice
Methodological detailsin vitro CD3+ T cells, Cxcr4 conditional knockout (CKO) arthritis mice models
- In vitro CD3+ T cells
- Cxcr4 conditional knockout (CKO) arthritis mice models
Main finding
As reported in the abstract
- Low dose MTX associated with down-regulated CXCR4 expression on patient peripheral T cells
- In vitro, low dose MTX significantly decreased transmigration via down-regulated CXCR4 expression in CD3+ T cells
- Low dose MTX increased genomic hypermethylation across Cxcr4 promoter region in CD3+ T cells
- Low dose MTX-mediated CXCR4 downregulation significantly improved pathological development in mouse arthritis models
- Cxcr4 CKO potentially alleviated joint and lung inflammation; clinical arthritis scores overall unchanged, except significant improvement on day 45 (recovery phase)
Original publication
Low dose methotrexate impaired T cell transmigration through down-regulating CXCR4 expression in rheumatoid arthritis (RA). Arthritis Res Ther. Published 30 September 2024. doi:10.
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