CD206+CD163+ macrophages residing within the inflamed RA synovium express inflammatory genes such as SPP1 (osteopontin) and SOD2 (a superoxide anion overproduced in joint inflammation) (42), and healthy synovial tissue macrophages, in contrast, express markers such as TREM2 and APOE, thought to play an important role in immunoregulation (43) (fig. Here, TREM2 is linked to rheumatoid arthritis.