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About the IL-12/23 Pathway

Shared Cytokines Across the Autoimmune Axis1-15

Shared Cytokines Across the Autoimmune Axis

Note: This is not intended to be a complete depiction of cells and cytokines possibly contributing to immune-mediated inflammatory conditions.
*Other cytokines that facilitate differentiation of Th17 cells include TGF-β, IL-1, and IL-6, while IL-23 promotes survival and expansion of the Th17 cells.12,13

ILC3=group 3 innate lymphoid cells; iNKT=invariant natural killer T cells; MAIT=mucosal-associated invariant T cells.

References:
  1. Boyapati R, et al. F1000 Prime Reports. 2015;7:44.
  2. Szilagyi A. Clin J Gastroenterol. 2020;13(2):139-152.
  3. Swanson GR, et al. Alcohol. 2010;44(3):223–228.
  4. Chandra S, Kronenberg M. Advances in Immunology. 2015;127:145-201.
  5. Chen F, et al. J Immunol. 2016;196(10):4390-4399.
  6. Tecchio C, et al. Front Immunol. 2014;5:508.
  7. De Winter BY, et al. Biochimica et Biophysica Acta. 2012;1822(1):66-73.
  8. Scher J. J Rheumatol. 2018;94:32-35.
  9. Scher J, et al. Arthritis Rheumatol. 2015;67(1):128-139.
  10. Manasson J, et al. Arthritis Rheumatol. 2020;72(4):645-657.
  11. Maillet J, et al. Joint Bone Spine. 2016;83(6):665-668.
  12. Boutet MA, et al. Int J Mol Sci. 2018;19(2):530.
  13. Eken A, Oukka M. Interleukin 23 in IBD Pathogenesis. New Insights into Inflammatory Bowel Disease. 2016. IntechOpen. doi:10.5772/64882.
  14. Gracey E, et al. Curr Opin Rheumatol. 2019;31(1):62-69.
  15. Toussirot E, Saas P. RMD Open. 2018;4(2):e000821.

Focus on IL-12/23 Pathways

Focus on IL-12/23 Pathways
  • There are several cytokines involved in the pathophysiology of ulcerative colitis and Crohn’s disease
  • Increased IL-12/IL-23 signaling and mutations in IL23R are linked to pathologic inflammation in relevant tissues for ulcerative colitis and Crohn’s disease
  • IL-12 and IL-23 activate receptors expressed on T cells and natural killer (NK) cells, driving proinflammatory effector cytokine signaling through this specific inflammatory pathway

Current as of March 2021

The safety and efficacy of the investigational use of these products have not been determined. There is no guarantee that the investigational uses listed will be filed with and/or approved for marketing by the FDA. For additional information, you may visit www.clinicaltrials.gov.

We are committed to finding new treatment options for patients with immune-mediated inflammatory diseases (IMIDs).

To learn more about currently recruiting studies, view the "Janssen IBD Clinical Studies" tab.

References:
  1. Tremelling M, Cummings F, Fisher SA, et al. IL23R variation determines susceptibility but not disease phenotype in inflammatory bowel disease. Gastroenterology. 2007;132(5):1657-1664.
  2. Duerr RH, Taylor KD, Brant SR, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006;314(5804):1461-1463.
  3. Nielsen OH, Kirman I, Rüdiger N, et al. Upregulation of interleukin-12 and -17 in active inflammatory bowel disease. Scand J Gastroenterol. 2003;38(2):180-185.
  4. El-Bassat H, AboAli L, Yamany S, et al. Interleukin-23p19 expression in patients with ulcerative colitis and its relation to disease severity. Advances in Digestive Medicine. 2015;3(3):88-94.
  5. Mohammadi M, Hayatbakhsh MM, Zahedi MJ, et al. Serum interleukin-23 levels in patients with ulcerative colitis. Iran J Immunol. 2011;8(3):183-188.
  6. Mirsattari D, Seyyedmajidi MR, Zojaji H, et al. The relation between the level of interleukin-23 with duration and severity of ulcerative colitis. Gastroenterol Hepatol Bed Bench. 2012;5(1):49-53.
  7. Chognard G, Bellemare L, Pelletier AN, et al. The dichotomous pattern of IL-12R and IL-23R expression elucidates the role of IL-12 and IL-23 in inflammation. PLoS One. 2014;9(2):e89092.
  8. Liu Z, Yadav PK, Xu X, et al. The increased expression of IL-23 in inflammatory bowel disease promotes intraepithelial and lamina propria lymphocyte inflammatory responses and cytotoxicity. J Leukoc Biol. 2011;89(4):597-606.
  9. Geremia A, Biancheri P, Allan P, et al. Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev. 2014;13(1):3-10.

Regulatory Cytokines of Th1 and Th17 Pathways1-4

Regulatory Cytokines of Th1 and Th17 Pathways
References:
  1. Boutet MA, et al. Int J Mol Sci. 2018;19(2):530.
  2. Hawkes JE, et al. J Immunol. 2018;201(6):1605-1613.
  3. Eken A, Oukka M. Interleukin 23 in IBD Pathogenesis. New Insights into Inflammatory Bowel Disease. 2016. IntechOpen. doi:10.5772/64882.
  4. Blanco P, et al. Cytokine Growth Factor Rev. 2008;19(1):41-52.
Hear more about the IL-23, Th1, and Th17 pathways with Dr Jonathan Sherlock
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Last Updated: May 2021