Ulcerative Colitis

JAK Pairings


Signalling Through JAKs

JAK-containing protein complexes mediate essential functions such as haematopoiesis and pathogen immunity through normal cytokine signalling.1,2

Excessive signalling through the JAK-STAT pathway results in atypical cytokine production and a cycle of chronic, relapsing inflammation, and potential damage in UC.1,3

JAK Combinations

Downstream effects of JAK-STAT pathway activation: In health and disease
Selective JAK pairings that mediate cytokine signalling

IBD pathogenesis*

Deleterious impact on wound healing5
Proinflammatory cytokine production in mucosa, tumour development6

Normal physiology*

Lymphocyte proliferation and homeostasis14,15
Adaptive immune response, intestinal homeostasis9
Humoral immunity, mucus production, anti-helminth defence15

Chronic intestinal epithelial inflammation5,7
Proinflammatory cytokine production5
Increased permeability of intestinal epithelial barrier5,8,9
Intestinal epithelial cell apoptosis and ulceration8,10
Epithelial cell proliferation and tumour growth (colorectal carcinogenesis)7,10,11

T-cell differentiation and inflammation3
Wound healing5
Defence from extracellular pathogens15
Lipid metabolism16

Epithelial cell death7
Disruption and loss of epithelial barrier function10

Antiviral and antimicrobial immunity15,16
Epithelial barrier protection5,17
Homeostasis of mucosal surfaces17

Not applicable

Erythropoiesis, myelopoiesis, and platelet production18
Intestinal epithelium protection5

IBD susceptibility12
Proinflammatory cytokine production13

Antiviral, antitumour defences15,16
Epithelial regeneration and maintenance of intestinal barrier5,9

* The physiological processes listed here are examples of the unique JAK roles and do not provide an exhaustive list.


JAK-STAT Pathway

Find out more about the JAK-STAT pathway in UC.

JAK-STAT Function

Find out why the JAK-STAT pathway is of particular therapeutic interest in UC.

IBD, inflammatory bowel disease; JAK, Janus kinase; STAT, signal transducer and activator of transcription; UC, ulcerative colitis.

REFERENCES: 1.Coskun M, Salem M, Pedersen J, Nielsen OH. Pharmacol Res. 2013;76:1-8. 2. Virtanen AT, Haikarainen T, Raivola J, Silvennoinen O. Bio Drugs. 2019;33(1):15-32. 3. Fernández-Clotet A, Castro-Poceiro J, Panés J. Curr Pharm Des. 2019;25(1):32-40. 4. Clark JD, Flanagan ME, Telliez JB. J Med Chem. 2014;57(12):5023-5038. 5. Flamant M, Rigaill J, Paul S, Roblin X. Drugs. 2017;77(10):1057-1068. 6. Neurath MF. Nat Immunol. 2019;20(8):970-979. 7. Neurath MF. Nat Rev Immunol. 2014;14(5):329-342. 8. De Vries LCS, Wildenberg ME, De Jonge WJ, D'Haens GRAM. J Crohn's Colitis. 2017;11(7):885-893. 9. Soendergaard C, Bergenheim FH, Bjerrum JT, Nielsen OH. Pharmacol Ther. 2018;192:100-111. 10. Bevivino G, Monteleone G. Expert Rev Gastroenterol Hepatol. 2018;12(9):907-915. 11. Lee SH, Kwon JE, Cho ML. Intest Res. 2018;16(1):26-42. 12. Li L-J, Gong C, Zhao M-H, Feng B-S. Wor Jour Gastroen. 2014;20(48):18177-18188. 13. Parks OB, Pociask DA, Hodzic Z, Kolls JK, Good M. Front Cell Dev Bio. 2016;85(3):1-13. 14. O'Shea JJ, Murray PJ. Immunity. 2008;28(4):477-487. 15. Heneghan AF, Pierre JF, Kudsk KA. JAK-STAT. 2013;2(4):e25530. 16. Banerjee S, Biehl A, Gadina M, Hasni S, Schwartz DM. Drugs. 2017;77(5):521-546. 17. Abraham C, Dulai PS, Vermeire S, Sandborn WJ. Gastroenterology. 2017;152(2):374-388.e4. 18. O’Shea JJ, Plenge R. Immunity. 2012;36(4):542-550.