A Receptor for the Heterodimeric Cytokine IL-23 Is Composed of IL-12R beta 1 and a Novel Cytokine Receptor Subunit, IL-23R

• Published in: The Journal of immunology (1950) Vol. 168; no. 11; pp. 5699 - 5708
• Main Authors: Parham, C, Chirica, M, Timans, J, Vaisberg, E, Travis, M, Cheung, J, Pflanz, S, Zhang, R, Singh, K P, Vega, F, To, W, Wagner, J, O'Farrell, A, McClanahan, T, Zurawski, S, Hannum, C, Gorman, D, Rennick, D M, Kastelein, R A, de Waal Malefyt, R, Moore, K W
• Format: Journal Article
• Language: English
• Published: 01.06.2002
• ISSN: 0022-1767
• DOI: 10.4049/jimmunol.168.11.5699

IL-23 is a heterodimeric cytokine composed of the IL-12p40 "soluble receptor" subunit and a novel cytokine-like subunit related to IL-12p35, termed p19. Human and mouse IL-23 exhibit some activities similar to IL-12, but differ in their capacities to stimulate particular populations of memory T cells. Like IL-12, IL-23 binds to the IL-12R subunit IL-12R beta 1. However, it does not use IL-12R beta 2. In this study, we identify a novel member of the hemopoietin receptor family as a subunit of the receptor for IL-23, "IL-23R." IL-23R pairs with IL-12R beta 1 to confer IL-23 responsiveness on cells expressing both subunits. Human IL-23, but not IL-12, exhibits detectable affinity for human IL-23R. Anti-IL-12R beta 1 and anti-IL-23R Abs block IL-23 responses of an NK cell line and Ba/F3 cells expressing the two receptor chains. IL-23 activates the same Jak-stat signaling molecules as IL-12: Jak2, Tyk2, and stat1, -3, -4, and -5, but stat4 activation is substantially weaker and different DNA-binding stat complexes form in response to IL-23 compared with IL-12. IL-23R associates constitutively with Jak2 and in a ligand-dependent manner with stat3. The ability of cells to respond to IL-23 or IL-12 correlates with expression of IL-23R or IL-12R beta 2, respectively. The human IL-23R gene is on human chromosome 1 within 150 kb of IL-12R beta 2.