Rheumatoid Arthritis

JAK-STAT Function

Function

Among other pathways, the JAK-STAT pathway is essential for normal immunological function1

Essential immunological functions depend on the dynamic equilibrium of the JAK-STAT pathway.1

Physiological disruptions and inflammatory diseases, such as RA, have been associated with deficient and excessive JAK-STAT pathway signalling, respectively.2-13


The importance of balanced JAK-STAT pathway signalling


Excessive cytokine signalling


Excessive cytokine signalling via certain JAK pairings is associated with typical signs of RA pathology, such as bone destruction, inflammation, and autoimmunity.14-16



Deficient cytokine signalling


A number of cytokines signal through JAK-STAT pathways by binding to their associated receptors.1

Understanding the JAK-STAT pathway and its role in essential immunological and physiological functions may help to advance the research of inflammatory diseases.1,17,18

Related

JAK Pairings

Learn more about JAK pairings

Treatment Guidelines

Explore treatment guidelines for patients with RA

HCP, healthcare provider; JAK, Janus kinase; RA, rheumatoid arthritis; STAT, signal transducer and activator of transcription.


REFERENCES

1. Villarino AV, Kanno Y, Ferdinand JR, O'Shea JJ. J Immunol. 2015;194(1):21-27. 2. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O'Shea JJ. Nat Rev Drug Discov. 2017;16(12):843-862. 3. Park SO, Wamsley HL, Bae K, et al. PLoS One. 2013;8(3):e59675. 4. Gotthardt D, Sexl V. Front Immunol. 2016;7:694. 5. Bottos A, Gotthardt D, Gill JW, et al. Nat Commun. 2016;7:12258. 6. Wang KS, Zorn E, Ritz J. Blood. 2001;97(12):3860-3866. 7. Hashizume M, Hayakawa N, Mihara M. Rheumatology (Oxford). 2008;47(11):1635-1640. 8. McInnes IB, Leung BP, Sturrock RD, Field M, Liew FY. Nat Med. 1997;3(2):189-195. 9. Ferrari-Lacraz S, Zanelli E, Neuberg M, et al. J Immunol. 2004;173(9):5818-5826. 10. González-Alvaro I, Domínguez-Jiménez C, Ortiz AM, et al. Arthritis Res Ther. 2006;8(4):R88. 11. Li J, Shen W, Kong K, Liu Z. Scand J Immunol. 2006;64(5):515-522. 12. Xing R, Yang L, Jin Y, et al. Scand J Immunol. 2016;83(1):64-71. 13. Kwok SK, Cho ML, Park MK, et al. Arthritis Rheum. 2012;64(3):740-751. 14. Dinesh P, Rasool M. J Cell Physiol. 2018;233(5):3918-3928. 15. Chen Z, Han Y, Gu Y, et al. J Immunol. 2013;190(12):5256-5266. 16. Schwartz DM, Bonelli M, Gadina M, O'Shea JJ. Nat Rev Rheumatol. 2016;12(1):25-36. 17. Winthrop KL. Nat Rev Rheumatol. 2017;13(4):234-243. 18. O’Shea JJ, Schwartz DM, Villarino AV, Gadina M, McInnes IB, Laurence A. Annu Rev Med. 2015;66:311-328.