CTLA4 and rheumatoid arthritis: In RA, Foxp3(+)CD4(+) T cells are subjected to conversion into TH17 cells, which is mediated by synovial fibroblast-derived IL-6 [110], and meanwhile, IFN-gamma cytokines, IL-4, and cytotoxic T lymphocyte-associated protein 4 (CTLA-4), produced by Th1, Th2, and respectively, Treg, regulate osteoclast differentiation.