Contribution of CD147-cyclophilin interactions to rheumatoid arthritis

CD147 is a transmembrane glycoprotein expressed on all leukocytes and is known to regulate leukocyte migration through its cell surface interaction with chemotactic extracellular cyclophilins. A potential role for CD147-cyclophilin interactions during inflammatory diseases, including rheumatoid arthritis (RA), is suggested from several studies. For example, the synovial fluid of RA patients contains high levels of extracellular cyclophilin A and reactive leukocytes expressing elevated CD147, which correlate with disease status. In the current studies we investigated the contribution of the chemotactic function of CD147-cyclophilin interactions to joint inflammation. Our data demonstrate that RA-relevant activated CD4+ T cells respond more efficiently to extracellular cyclophilins when compared to non-RA relevant naive CD4+ T cells. Additionally, we show that pro-inflammatory leukocytes lose their ability to migrate in response to cyclophilin A in vitro when treated with anti-CD147 mAb. Furthermore, targeting the CD147-cyclophilin interaction in vivo can reduce the development of collagen induced arthritis (CIA), a mouse model for RA, by 75-90%. Such findings suggest that CD147-cyclophilin interactions might contribute to the pathogenesis of RA by promoting the recruitment of leukocytes into joint tissues.