Interleukin-23 binds interleukin-23 receptor

Stable Identifier
R-HSA-447130
Type
Reaction [omitted]
Species
Homo sapiens
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Interleukin-23 (IL23) is a complex of Interleukin-23 subunit alpha (IL23A) and Interleukin-12 subunit beta (IL12B, IL-12p40). IL12B is also a component of Interleukin-12 (IL12) (Oppmann et al. 2000, Lupardus & Garcia et al. 2008).
The Interleukin-23 receptor consists of Interleukin 23 receptor subunit (IL23R) and Interleukin 12 receptor subunit beta 1 (IL12RB1). IL12RB1 is shared with the Interleukin-12 receptor.
The Interleukin-23 receptor binds IL23 but does not interact with IL12. IL12RB1 is required to confer IL23 responsiveness in cells (Parham et al. 2002).
IL23 is produced by antigen presenting cells and promotes the expansion and survival of a distinct lineage of T cells called T helper 17 (Th17) (Langrish et al. 2005). Increasing evidence supports the idea that Th17 cells do not require traditional T helper 1(Th1) or T helper 2 (Th2) transcription factors or regulatory genes, and that their differentiation is inhibited by Interferon-gamma (IFNG) and Interleukin 4 (IL4) (Hoeve et al. 2006).
Naive T cells cultured in the presence of Transforming growth factor beta 1(TGFB1) and Interleukin 6 (IL6) and in the absence of IFNG or IL4 are polarized to Th17 cells and upregulate IL23R (Veldhoen et al. 2006).

Subsequently, IL23 appears to be required for the expansion and survival of Th17 cells. Like Th1 and Th2 cells, Th17 cells remain committed to their lineage, even in the presence of other Th polarizing cytokines (Harrington et al. 2005).
The Interleukin 23 receptor ligand interaction has been shown to activate Signal transducer and activator of transcription 3 (STAT3), resulting in binding to the Interleukin 17A(IL17A) and Interleukin 17F (IL17F) promoters. The T cell response activated by Interleukin 23 heterodimer is attenuated by Suppressor of cytokine signaling 3 (SOCS3), which acts as a feedback inhibitor to regulate Th17 cells (Chen et al. 2006).

Knockout mice deficient in either IL12B or IL23A, or in either subunit of the Interleukin-23 receptor (IL23R or IL12RB1) have reduced symptoms of multiple sclerosis and inflammatory bowel disease suggesting that IL23 is involved in these inflammatory diseases (Kikly et al. 2006).
As it is not clear whether the dimeric receptor can form in the absence of ligand, formation of the receptor dimer is represented here as a black box event.

Literature References
PubMed ID Title Journal Year
12023369 A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R

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

J Immunol 2002
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