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. 2020 Apr 3;9(4):880. doi: 10.3390/cells9040880

Figure 6.

Figure 6

Molecular mode of action of Janus activated kinase (JAK) inhibitors. Binding of pro-inflammatory cytokines (e.g., IL-6, common γ-chain-containing cytokines (e.g., IL-2 or IL-15), type I and II interferons, or granulocyte-monocyte colony stimulating factor (GM-CSF)) to their respective receptors on the surface of immune cells triggers the recruitment of JAKs. JAKs subsequently phosphorylate the intracytoplasmic parts of the respective receptors, inducing the phosphorylation, auto-homodimerization, and nuclear translocation of different signal transducer and activator of transcription (STAT) molecules. In the respective cell’s nucleus STAT dimers promote the expression of many pro-inflammatory genes that initiate and sustain joint inflammation and tissue damage. The targeted DMARDs tofacitinib and baricitinib inhibit this activation of JAKs and thereby prevent immune cell activation and subsequent inflammatory responses.