Essential immunological functions depend on the dynamic equilibrium of the JAK-STAT pathway.1
Deficient or excessive JAK-STAT pathway signalling has been associated with physiological disruptions and
inflammation, respectively.
Understanding the JAK-STAT pathway and its role in essential functions may help to advance the research
of inflammatory diseases, such as UC.
• Multiple proinflammatory cytokine pathways are implicated in the pathogenesis of UC9
• Simultaneous targeting of multiple cytokines has demonstrated efficacy for the management of UC9
• Many of the proinflammatory cytokines implicated in UC signal through JAK1-containing protein complexes6,10
• Cytokines implicated in UC pathogenesis that do not signal directly through JAK1, such as IL-33, are still directly
associated with the activity of JAK1-dependent cytokines, such as IL-4 and IFNγ11
Not all JAK1-, JAK2-, JAK3-, or TYK2-associated cytokines are included here. This is not an exhaustive list.
EPO, erythropoeitin; G-CSF, granulocyte colony-stimulating factor; GH, growth hormone; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; IL, interleukin; LIF, leukemia inhibitory factor; OSM, oncostatin M; TPO, thrombopoeitin.
A focus on selectivity may be key to UC-associated inflammation.14
IBD, inflammatory bowel disease; IFN, interferon; IL, interleukin; JAK, Janus kinase; STAT, signal transducer and activator of transcription; TYK, tyrosine kinase; UC, ulcerative colitis.
* Note that some of the observations pertaining to these potential benefits were described in mouse studies.
REFERENCES: 1.Villarino AV, Kanno Y, Ferdinand JR, O'Shea JJ. J Immunol. 2015;194(1):21-27. 2. Wang KS, Zom E, Ritz J. Blood. 2001;97(12):3860-3866. 3. Coskun M, Salem M, Pedersen J, Nielsen OH. Pharmacol Res. 2013;76:1-8. 4. Bottos A, Gotthardt D, Gill JW, et al. Nat Commun. 2016;7:12258. 5. Gotthardt D, Sexl V. Front Immunol. 2017;7:694. 6. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O'Shea JJ. Nat Rev Drug Discov. 2017;16(12):843-862. 7. Neurath MF. Nat Rev Immunol. 2014;14(5):329-342. 8. O'Shea JJ, Schwartz DM, Villarino AV, Gadina M, McInnes IB, Laurence A. Annu Rev Med. 2015;66:311-328. 9. Danese S, Argollo M, Le Berre C, Peyrin-Biroulet L. Gut. 2019;68(10):1893-1899. 10. Virtanen AT, Haikarainen T, Raivola J, Silvennoinen O. BioDrugs. 2019;33(1):15-32. 11. Pinto SM, Subbannayya Y, Rex DAB, et al. J Cell Commun Signal. 2018;12(3):615-624. 12. Salas A, Hernandez-Rocha C, Duijvestein M, et al. Nat Rev Gastroenterol Hepatol. 2020;17(6):323-337. 13. Flamant M, Rigaill J, Paul S, Roblin X. Drugs. 2017;77(10):1057-1068. 14. Fernández-Clotet A, Castro-Poceiro J, Panés J. Curr Pharm Des. 2019;25(1):32-40.
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