Figure 3. ACPA with specificity to citrullinated vimentin induces the differentiation of OC precursors as well as promotes the inflammatory response in RA. The vimentin located in the cytoplasm of OC precursors and OCs is citrullinated by PDA enzymes in the presence of calcium and it is expressed on the cell surface. ACPA, which appears to have been generated in the inflammatory environment of lung or gingiva, binds to this citrullinated vimentin and it increases the expression of IL-8 from OC precursors and OCs. IL-8 increases the differentiation of OC precursors in an autocrine manner and is also involved in the recruitment of neutrophils as a chemokine. NETs formation by recruited neutrophils acts to amplify the inflammation of synovial tissue and thus to develop RA.
