RA clinical trials showed that the CTLA-4-Ig fusion protein Abatacept can reduce synovial inflammation and pathology by selectively modulating CD28, CD80, and CD86 co-stimulation signals in T cells (110, 111), which further confirmed that the functions of CTLA-4 in immune regulation, especially in Treg cells, play a very important role in controlling the onset and progression of RA (Figure 3A). This evidence concerns the gene CTLA4 and rheumatoid arthritis.