Fig. 2

E6011 targets CX3CR1+ cells in the inflammatory sites in RA. The interaction of the osteoclast precursor with osteoblasts via FKN-CX3CR1 promotes the osteoclast differentiation. The macrophage may be recruited by FLS-induced chemokine production through FKN-CX3CR1. In turn, the macrophage helps to activate the synovial sublining fibroblasts through the production of inflammatory cytokines such as TNF-α. CX3CR1 expressed on the cytotoxic effector CD4+ T cell binds to FKN on the fibroblast. And then, T cell-FLS communication activates the TNF-α production. TNF-α up-regulates FKN production as a growth factor of synovial fibroblasts, and TNF-α also induces the MMP3 expression, matrix metalloproteinase. Taken together, the interaction of FLS with the macrophage and T cells through FKN-CX3CR1 may contribute to the enhancement of inflammation and joint destruction