Rheumatoid Arthritis

JAK Pairings

Overview

Cytokines can signal through many pathways, including the JAK-STAT pathway. Normal cytokine signalling through JAK pairs is essential for bodily functions, such as providing immunity against pathogens and haematopoiesis.1

In RA, increased cytokine presence creates a chronic signalling loop through the JAK-STAT pathway, which may lead to overproduction of proinflammatory cytokines and activation of immune cells that can result in tissue destruction, systemic inflammation, and escalating cycles of autoimmunity.2-6

Selective JAK pairings that mediate cytokine signalling


RA pathogenesis
 


Inflammation
Blood vessel formation
Bone destruction
Autoimmunity6-8

Normal physiology
 


Lymphocyte proliferation1 Differentiation of NK cells1,14


Pain and inflammation
Blood vessel and pannus formation
Bone and cartilage destruction
Autoimmunity
Systemic symptoms8-10


T cell differentiation and
homeostasis
Granulocyte production1,14


Inflammation
Synovial tissue remodelling
Autoimmunity8,11,12


Innate antiviral defence1


Autoimmunity13


Red blood cell production
Bone marrow production
Platelet production1


Inflammation
Synovial tissue remodelling
Autoimmunity8


Innate antiviral defence
Antitumour1

JAK1 pairs are involved in signalling for proinflammatory cytokines implicated in RA pathology.8,14-16

Related

JAK-STAT Pathway

Learn more about the JAK-STAT pathway

JAK-STAT Function

Learn more about the function of the JAK-STAT pathway

Discover our product information for rheumatoid arthritis

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


REFERENCES

1. Winthrop KL. Nat Rev Rheumatol. 2017;13(4):234-243. 2. Hodge JA, Kawabata TT, Krishnaswami S, et al. Clin Exp Rheumatol. 2016;34(2):318-328. 3. McInnes IB, Schett G. Nat Rev Immunol. 2007;7(6):429-442. 4. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O'Shea JJ. Nat Rev Drug Discov. 2017;16(12):843-862. 5. Schett G. Rheumatology (Oxford). 2018;57(suppl 2):ii43-ii50. 6. Dinesh P, Rasool M. J Cell Physiol. 2018;233(5):3918-3928. 7. Chen Z, Han Y, Gu Y, et al. J Immunol. 2013;190(12):5256-5266. 8. Schwartz DM, Bonelli M, Gadina M, O'Shea JJ. Nat Rev Rheumatol. 2016;12(1):25-36. 9. Srirangan S, Choy EH. Ther Adv Musculoskelet Dis. 2010;2(5):247-256. 10. Boettger MK, Leuchtweis J, Kümmel D, Gajda M, Bräuer R, Schaible HG. Arthritis Res Ther. 2010;12(4):R140. 11. Schurgers E, Billiau A, Matthys P. J Interferon Cytokine Res. 2011;31(12):917-926. 12. Aletaha D, Smolen JS. JAMA. 2018;320(13):1360-1372. 13. Lotfi N, Thome R, Rezaei N, et al. Front Immunol. 2019;10:1265. 14. Clark JD, Flanagan ME, Telliez JB. J Med Chem. 2014;57(12):5023-5038. 15. Choy EH. Rheumatology (Oxford). 2019;58(6):953-962. 16. Virtanen AT, Haikarainen T, Raivola J, Silvennoinen O. BioDrugs. 2019;33(1):15-32.