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
Inflammation4
Deleterious impact on wound healing5
Proinflammatory cytokine production in mucosa, tumour development6
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
Growth16
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.
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.
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