Rheumatoid Arthritis

Cytokine signalling and the JAK-STAT pathway


The JAK-STAT pathway mediates both inflammatory and normal physiological functions.1-3
Emerging research continues to improve our understanding of how the JAK-STAT pathway plays important roles in inflammatory diseases (e.g., RA) and normal physiological functions.1-4
Four JAK proteins form pairs to propagate cytokine signalling—JAK1, JAK2, JAK3, and TYK2.2
A number of cytokines signal through JAK-STAT pathways by binding to their associated receptors.1
Each JAK protein may play a unique role in the effectiveness of certain cytokines.5-9

The four JAK proteins are activated by and propagate the signalling of numerous key proinflammatory cytokines, including IL-6, IL-7, IL-15, IL-21, GM-CSF, and IFN-γ.2

Four JAK proteins pair to facilitate the actions of certain cytokines.3,6,10,11

Key cytokines of the JAK-STAT pathway2,*

[P] = phosphorylation.

[C] [C] [C] [C] [C] = cytokines bound to receptor.

JAK protein pairs form specific JAK-STAT pathways that play a unique role in normal physiological functions.10-13

GM-CSF, granulocyte-macrophage colony-stimulating factor; HCP, healthcare provider; IFN, interferon; IL, interleukin; JAK, Janus kinase; NK, natural killer; RA, rheumatoid arthritis; STAT, signal transducer and activator of transcription.

* Not all cytokines are included in this graphic.


1. McInnes IB, Schett G. Nat Rev Immunol. 2007;7(6):429-442. 2. Winthrop KL. Nat Rev Rheumatol. 2017;13(4):234-243. 3. O’Shea JJ, O'Shea JJ, Schwartz DM, Villarino AV, Gadina M, McInnes IB, Laurence A. Annu Rev Med. 2015;66:311-328. 4. Malemud C. Int J Mol Sci. 2017;18(3). pii: E484. 5. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O'Shea JJ. Nat Rev Drug Discov. 2017;16(12):843-862. 6. Choy EH. Rheumatology (Oxford). 2019;58(6):953-962. 7. Gadina M, Johnson C, Schwartz D. J Leukoc Biol. 2018;104(3):499-514. 8. Isomäki P, Junttila I, Vidqvist KL, Korpela M, Silvennoinen O. Rheumatology (Oxford). 2015;54(6):1103-1113. 9. McInnes IB, Schett G. N Engl J Med. 2011;365(23):2205-2219. 10. Clark JD, Flanagan ME, Telliez JB. J Med Chem. 2014;57(12):5023-5038. 11. Malemud CJ. Ther Adv Musculoskelet Dis. 2018;10(5-6):117-127. 12. Ghoreschi K, Laurence A, O'Shea JJ. Immunol Rev. 2009;228(1):273-287. 13. Gadina M, Le MT, Schwartz DM. Rheumatology (Oxford). 2019;58(suppl 1):i4-i16. 14. Wu Y, Tian Z, Wei H. Front Immunol. 2017;8:930. 15. Maeda K, Malykhin A, Teague-Weber BN, Sun XH, Farris AD, Coggeshall KM. Blood. 2009;113(19):4534-4540. 16. Morris R, Kershaw NJ, Babon J. Protein Sci. 2018;(27):1984-2009. 17. Tang Y, Liu W, Wang W, et al. Cardiovasc Drugs Ther. 2020;34(2):145-152. 18. Takaoka A, Yanai H. Cell Microbiol. 2006;8(6):907-922.



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