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1. McInnes IB, Schett Nat Rev Immunol. 2007;7(6):429-442.

2. Winthrop KL. Nat Rev Rheumatol. 2017;13(4):234-243.

3. 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. Sciumè G, Le MT, Gadina M. Front Immunol. 2017;8:438.

11. Clark JD, Flanagan ME, Telliez JB. J Med Chem. 2014;57(12):5023-5038.

12. Malemud CJ. Ther Adv Musculoskelet Dis. 2018;10(5-6):117-127.

13. Choy EH. Rheumatology (Oxford). 2019;58:953-962.

14. Ghoreschi K, Laurence A, O'Shea JJ. Immunol Rev. 2009;228(1):273-287.

15. Gadina M, Le MT, Schwartz DM. Rheumatology (Oxford). 2019;58(suppl 1):i4-i16.

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 TYK2.1
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 effect of certain cytokines.1,6-9

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.1,10

Key cytokines of the JAK-STAT pathway2,*

SWIPE TO EXPLORE

JAK protein pairs form specific JAK-STAT pathways that play a unique role in normal physiological functions.11-14

Lymphocyte proliferation2

Differentiation of NK cells2,11

T-cell differentiation and homeostasis

Granulocyte production2,11

Innate antiviral defence2

Red blood cell production

Bone marrow production

Platelet production2

Innate antiviral defence

Antitumour2

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References: 1. McInnes IB, et al. Nat Rev Immunol. 2007;7:429-442. 2. Winthrop KL. Nat Rev Rheumatol. 2017;13:234-243. 3. O’Shea JJ, et al. Annu Rev Med. 2015;66:311-328. 4. Malemud CJ. Int J Mol Sci. 2017;18(3). Pii:E48. 5. Schwartz DM, et al. Nat Rev Drug Discov. 2017;16:843-862. 6. Choy EH. Rheumatology (Oxford). 2019;58(6):953-962. 7. Gadina M, et al. J Leukoc Biol. 2018;104:499-514. 8. Isomäki P, et al. Rheumatology (Oxford). 2015;54:1103-1113. 9. McInnes IB, et al. N Engl J Med. 2011;365:2205-2219. 10. Sciume G, et al. Front Immunol. 2017;8:438. 11. Clark JD, et al. J Med Chem. 2014;57:5023-5038. 12. Malemud CJ. Ther Adv Musculoskelet Dis. 2018;10:117-127. 13. Ghoreschi K, et al. Immunol Rev. 2009;228(1):273-287. 14. Gadina M, et al. Rheumatology (Oxford). 2019;58(suppl 1):i4-i16.