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A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R
- Source :
- Scopus-Elsevier
- Publication Year :
- 2002
-
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.
- Subjects :
- Immunology
Interleukin 5 receptor alpha subunit
Molecular Sequence Data
Biology
Gamma-aminobutyric acid receptor subunit alpha-1
Interleukin-23
Interleukin 10 receptor, alpha subunit
Mice
Interleukin-4 receptor
Immunology and Allergy
Animals
Humans
Amino Acid Sequence
Receptors, Cytokine
Common gamma chain
Mice, Inbred BALB C
Interleukins
Receptors, Interleukin-12
Receptors, Interleukin
Glycoprotein 130
Molecular biology
Interleukin-12
Interleukin 10
Interleukin-21 receptor
Interleukin-23 Subunit p19
Dimerization
Signal Transduction
Subjects
Details
- ISSN :
- 00221767
- Volume :
- 168
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....4e6c8fd3f2bd802c3f1e9d859a737054