Crystal structure of IL-12B
|Alt. symbols||CLMF2, NKSF2, p40|
|Locus||Chr. 5 q31.1-33.1|
|interleukin 23, alpha subunit p19|
|Locus||Chr. 12 q13.13|
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. A functional receptor for IL-23 (the IL-23 receptor) has been identified and is composed of IL-12R β1 and IL-23R.
Prior to the discovery of IL-23, IL-12 had been proposed to represent a key mediator of inflammation in mouse models of inflammation. 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.
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. 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, intestinal inflammation, and psoriasis.
- Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA (Jan 2001). "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. PMID 11114383. doi:10.1016/S1074-7613(00)00070-4.
- Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, Pflanz S, Zhang R, Singh KP, Vega F, To W, Wagner J, O'Farrell AM, McClanahan T, Zurawski S, Hannum C, Gorman D, Rennick DM, Kastelein RA, de Waal Malefyt R, Moore KW (2000). "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. PMID 12023369. doi:10.4049/jimmunol.168.11.5699.
- Leonard JP, Waldburger KE, Goldman SJ (Jan 1995). "Prevention of experimental autoimmune encephalomyelitis by antibodies against interleukin 12". Journal of Experimental Medicine. 181 (1): 381–6. PMC . PMID 7528773. doi:10.1084/jem.181.1.381.
- Becher B, Durell BG, Noelle RJ (Aug 2002). "Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12". Journal of Clinical Investigation. 110 (4): 493–7. PMC . PMID 12189243. doi:10.1172/JCI15751.
- Cua DJ; Sherlock J; Chen Y; Murphy CA; Joyce B; Seymour B; Lucien L; To W; Kwan S; Churakova T; Zurawski S; Wiekowski M; Lira SA; Gorman D; Kastelein RA. Sedgwick JD (Feb 2003). "Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain". Nature. 421 (6924): 744–8. PMID 12610626. doi:10.1038/nature01355.
- Murphy CA, Langrish CL, Chen Y, Blumenschein W, McClanahan T, Kastelein RA, Sedgwick JD, Cua DJ (Dec 2002). "Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation". Journal of Experimental Medicine. 198 (12): 1951–7. PMC . PMID 14662908. doi:10.1084/jem.20030896.
- Yen D1, Cheung J, Scheerens H, Poulet F, McClanahan T, McKenzie B, Kleinschek MA, Owyang A, Mattson J,Blumenschein W, Murphy E, Sathe M, Cua DJ, Kastelein RA, Rennick D. (May 2006). "IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6". Journal of Clinical Investigation. 116 (5): 1310–6. PMC . PMID 16670770. doi:10.1172/JCI21404.
- Kullberg MC, Jankovic D, Feng CG, Hue S, Gorelick PL, McKenzie BS, Cua DJ, Powrie F, Cheever AW, Maloy KJ, Sher A (Oct 2006). "IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent colitis". Journal of Experimental Medicine. 203 (11): 2485–94. PMC . PMID 17030948. doi:10.1084/jem.20061082.
- Hue S, Ahern P, Buonocore S, Kullberg MC, Cua DJ, McKenzie BS, Powrie F, Maloy KJ (2006). "Interleukin-23 drives innate and T cell-mediated intestinal inflammation". Journal of ExperimentalMedicine. 203 (11): 2473–83. PMC . PMID 17030949. doi:10.1084/jem.20061099.
- Chan JR, Blumenschein W, Murphy E, Diveu C, Wiekowski M, Abbondanzo S, Lucian L, Geissler R, Brodie S, Kimball AB, Gorman DM, Smith K, de Waal Malefyt R, Kastelein RA, McClanahan TK, Bowman EP (Oct 2006). "IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis.". Journal of Experimental Medicine. 203 (12): 2577–87. PMC . PMID 17074928. doi:10.1084/jem.20060244.