A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rβ1 and a novel cytokine receptor subunit, IL-23R

Christi Parham, Madaline Chirica, Jacqueline Timans, Elena Vaisberg, Marilyn Travis, Jeanne Cheung, Stefan Pflanz, Rebecca Zhang, Komal P. Singh, Felix Vega, Wayne To, Janet Wagner, Anne Marie O'Farrell, Terrill McClanahan, Sandra Zurawski, Charles Hannum, Daniel Gorman, Donna M. Rennick, Robert A. Kastelein, Rene De Waal MalefytKevin W. Moore

Research output: Contribution to journalArticlepeer-review

993 Scopus citations

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 statl, -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.

Original languageEnglish (US)
Pages (from-to)5699-5708
Number of pages10
JournalJournal of Immunology
Volume168
Issue number11
DOIs
StatePublished - Jun 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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