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A Receptor for the Heterodimeric Cytokine IL-23 Is Composed of IL-12Rβ1 and a Novel Cytokine Receptor Subunit, IL-23R

Parham, Christi, Chirica, Madaline, Timans, Jacqueline, Vaisberg, Elena, Travis, Marilyn, Cheung, Jeanne, Pflanz, Stefan, Zhang, Rebecca, Singh, Komal P, Vega, Felix, To, Wayne, Wagner, Janet, O’Farrell, Anne-Marie, McClanahan, Terrill, Zurawski, Sandra, Hannum, Charles, Gorman, Daniel, Rennick, Donna M, Kastelein, Robert A, de Waal Malefyt, Rene, Moore, Kevin W·2002·The Journal of Immunology

Abstract

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-12Rβ1. However, it does not use IL-12Rβ2. 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-12Rβ1 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-12Rβ1 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-12Rβ2, respectively. The human IL-23R gene is on human chromosome 1 within 150 kb of IL-12Rβ2.

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Metadata

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.-M., McClanahan, T., Zurawski, S., Hannum, C., Gorman, D., Rennick, D. M., Kastelein, R. A., de Waal Malefyt, R., & Moore, K. W.
Venue
The Journal of Immunology
Published
2002-06-01
Volume
168
Issue
11
Pages
5699-5708
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W1847326477
Cited by
1,296
References
3
FWCI
18.51
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: A Receptor for the Heterodimeric Cytokine IL-23 Is Composed of IL-12Rβ1 and a Novel Cytokine Receptor Subunit, IL-23R. https://app.cochat.ai/papers/10.4049/jimmunol.168.11.5699
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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.-M., McClanahan, T., Zurawski, S., Hannum, C., Gorman, D., Rennick, D. M., Kastelein, R. A., . . . Moore, K. W. (2002). A Receptor for the Heterodimeric Cytokine IL-23 Is Composed of IL-12Rβ1 and a Novel Cytokine Receptor Subunit, IL-23R. The Journal of Immunology. https://doi.org/10.4049/jimmunol.168.11.5699

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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