Recruitment of CD16⁺ monocytes into synovial tissues is mediated by fractalkine and CX3CR1 in rheumatoid arthritis patients

CD16⁺ monocytes, identified as a minor population of monocytes in human peripheral blood, have been implicated in several inflammatory diseases, including rheumatoid arthritis (RA). Fractalkine (FKN, CX3CL1), a member of the CX3 C subfamily, is induced by pro-inflammatory cytokines, while a receptor for FKN, CX3CR1, is capable of mediating both leukocyte migration and firm adhesion. Here, we investigated the role of FKN and CX3CR1 in activation of CD16⁺ monocytes and their recruitment into synovial tissues in RA patients. High levels of soluble FKN were detected in the synovial fluid and sera of RA patients. Circulating CD16⁺ monocytes showed a higher level of CX3CR1 expression than CD16^- monocytes in both RA patients and healthy subjects. High level expression of CX3CR1 was also seen in CD16 ⁺ monocytes localized to the lining layer in RA synovial tissue. In the in vitro culture experiments, IL-10 induced CX3CR1 expression on the surface of monocytes, and TNFα induced membrane-bound FKN as well as soluble FKN expression in synovial fibroblasts. Moreover, soluble FKN was capable of inducing IL-1β and IL-6 by activated monocytes. These results suggest that FKN might preferentially mediate migration and recruitment of CD16⁺ monocytes, and might contribute to synovial tissue inflammation. Copyright