Fig. 4.

Roles of the JAK-STAT pathway in the pathogenesis of rheumatoid arthritis and recently approved JAK inhibitors. Abnormal JAK-STAT signaling induced by multiple cytokines is regarded as the essential pathogenesis of RA. The interaction of many cytokines (including IL-1, IL-17, IL-12, IL-23, IL-6, TNF-α, and IFN-γ) and the JAK-STAT pathway mediates inflammatory responses in the synovium and causes joint destruction. There are several JAK inhibitors approved for RA treatment, including tofacitinib, baricitinib, filgotinib, upadacitinib, peficitinib, and decernotinib. The dotted lines indicate negative regulation