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Interleukin-23 (IL-23) is a heterodimeric cytokine composed of an IL12B (IL-12p40) subunit (that is shared with IL12) and the IL23A (IL-23p19) subunit.[1] A functional receptor for IL-23 (the IL-23 receptor) has been identified and is composed of IL-12R β1 and IL-23R.[2]

IL12b Crystal Structure.rsh.png
Crystal structure of IL-12B
Alt. symbolsCLMF2, NKSF2, p40
NCBI gene3593
Other data
LocusChr. 5 q31.1-33.1
interleukin 23, alpha subunit p19
NCBI gene51561
Other data
LocusChr. 12 q13.13



IL-23 was first described by Robert Kastelein and colleagues at the DNAX research institute using a combination of computational, biochemical and cellular immunology approaches.[1]


IL-23 is a proinflammatory cytokine. IL-23 has been shown to be a key cytokine for Th17 maintenance and expansion. Th17 are polarised by IL-6 and TGF-β which activate Th17 transcription factor RORγt. IL-23 stabilises RORγt and thus enables Th17 to properly function and release their effector cytokines such as IL-17, IL-21, IL-22 and GM-CSF which mediate protection against extracellular parasites (fungi and bacteria) and participate in barrier immunity. [3] Similar effects as IL-23 has on Th17 cells were described on type 3 innate lymphoid cells which actively secrete Th17 cytokines upon IL-23 stimulation. [4] NK cells express IL-23 receptor too. They respond with increased IFN-γ secretion and enhanced antibody-dependent cellular cytotoxicity. IL-23 also induces proliferation of CD4 memory T cells (not naïve cells). [5] Along with mentioned proinflammatory effects IL-23 promotes angiogenesis. [6] 

IL-23 is mainly secreted by activated dendritic cells, macrophages or monocytes. Secretion is stimulated by an antigen stimulus recognised by a pattern recognition receptor. [7] IL-23 imbalance and increase is associated with autoimmune and cancerous diseases. It is thus a target for therapeutic research. [3]

Prior to the discovery of IL-23, IL-12 had been proposed to represent a key mediator of inflammation in mouse models of inflammation.[8] However, many studies aimed at assessing the role of IL-12 had blocked the activity of IL-12p40, and were therefore not as specific as thought. Studies which blocked the function of IL-12p35 did not produce the same results as those targeting IL-12p40 as would have been expected if both subunits formed part of IL-12 only.[9]

The discovery of an additional potential binding partner for IL-12p40 led to a reassessment of this role for IL-12. Seminal studies in experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis, showed that IL-23 was responsible for the inflammation observed, not IL-12 as previously thought.[10] Subsequently, IL-23 was shown to facilitate development of inflammation in numerous other models of immune pathology where IL-12 had previously been implicated including models of arthritis,[11] intestinal inflammation,[12][13][14] and psoriasis.[15] Ustekinumab, a monoclonal antibody directed against this cytokine, is used clinically to treat certain autoimmune conditions.[16]


IL-23 heterodimer binds the receptor complex - p19 subunit binds IL-23R while p40 subunit binds IL-12RB1 which leads to recruitment of Janus kinase 2 and Tyrosine kinase 2 kinases. Janus kinase 2 and Tyrosine kinase 2 transduce the signal and phosphorylate STAT3 and STAT4. STATs dimerise and activate transcription of target genes in nucleus. STAT3 is responsible for key Th17 development attributes like RORγt expression or transcription of Th17 cytokines.[3] 


  1. ^ a b Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, et al. (November 2000). "Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12". Immunity. 13 (5): 715–25. doi:10.1016/S1074-7613(00)00070-4. PMID 11114383.
  2. ^ Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, et al. (June 2002). "A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R". Journal of Immunology. 168 (11): 5699–708. doi:10.4049/jimmunol.168.11.5699. PMID 12023369.
  3. ^ a b c Tang C, Chen S, Qian H, Huang W (February 2012). "Interleukin-23: as a drug target for autoimmune inflammatory diseases". Immunology. 135 (2): 112–24. doi:10.1111/j.1365-2567.2011.03522.x. PMC 3277713. PMID 22044352.
  4. ^ Zeng B, Shi S, Ashworth G, Dong C, Liu J, Xing F (April 2019). "ILC3 function as a double-edged sword in inflammatory bowel diseases". Cell Death & Disease. 10 (4): 315. doi:10.1038/s41419-019-1540-2. PMC 6453898. PMID 30962426.
  5. ^ Li Y, Wang H, Lu H, Hua S (2016). "Regulation of Memory T Cells by Interleukin-23". International Archives of Allergy and Immunology. 169 (3): 157–62. doi:10.1159/000445834. PMID 27100864.
  6. ^ Langowski JL, Zhang X, Wu L, Mattson JD, Chen T, Smith K, et al. (July 2006). "IL-23 promotes tumour incidence and growth". Nature. 442 (7101): 461–5. Bibcode:2006Natur.442..461L. doi:10.1038/nature04808. PMID 16688182.
  7. ^ Re F, Strominger JL (October 2001). "Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells". The Journal of Biological Chemistry. 276 (40): 37692–9. doi:10.1074/jbc.M105927200. PMID 11477091.
  8. ^ Leonard JP, Waldburger KE, Goldman SJ (January 1995). "Prevention of experimental autoimmune encephalomyelitis by antibodies against interleukin 12". The Journal of Experimental Medicine. 181 (1): 381–6. doi:10.1084/jem.181.1.381. PMC 2191822. PMID 7528773.
  9. ^ Becher B, Durell BG, Noelle RJ (August 2002). "Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12". The Journal of Clinical Investigation. 110 (4): 493–7. doi:10.1172/JCI15751. PMC 150420. PMID 12189243.
  10. ^ Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, et al. (February 2003). "Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain". Nature. 421 (6924): 744–8. Bibcode:2003Natur.421..744C. doi:10.1038/nature01355. PMID 12610626.
  11. ^ Murphy CA, Langrish CL, Chen Y, Blumenschein W, McClanahan T, Kastelein RA, et al. (December 2003). "Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation". The Journal of Experimental Medicine. 198 (12): 1951–7. doi:10.1084/jem.20030896. PMC 2194162. PMID 14662908.
  12. ^ Yen D, Cheung J, Scheerens H, Poulet F, McClanahan T, McKenzie B, et al. (May 2006). "IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6". The Journal of Clinical Investigation. 116 (5): 1310–6. doi:10.1172/JCI21404. PMC 1451201. PMID 16670770.
  13. ^ Kullberg MC, Jankovic D, Feng CG, Hue S, Gorelick PL, McKenzie BS, et al. (October 2006). "IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent colitis". The Journal of Experimental Medicine. 203 (11): 2485–94. doi:10.1084/jem.20061082. PMC 2118119. PMID 17030948.
  14. ^ Hue S, Ahern P, Buonocore S, Kullberg MC, Cua DJ, McKenzie BS, et al. (October 2006). "Interleukin-23 drives innate and T cell-mediated intestinal inflammation". The Journal of Experimental Medicine. 203 (11): 2473–83. doi:10.1084/jem.20061099. PMC 2118132. PMID 17030949.
  15. ^ Chan JR, Blumenschein W, Murphy E, Diveu C, Wiekowski M, Abbondanzo S, et al. (November 2006). "IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis". The Journal of Experimental Medicine. 203 (12): 2577–87. doi:10.1084/jem.20060244. PMC 2118145. PMID 17074928.
  16. ^ Cingoz O (2009). "Ustekinumab". mAbs. 1 (3): 216–21. doi:10.4161/mabs.1.3.8593. PMC 2726595. PMID 20069753.