TY - JOUR
T1 - A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rβ1 and a novel cytokine receptor subunit, IL-23R
AU - Parham, Christi
AU - Chirica, Madaline
AU - Timans, Jacqueline
AU - Vaisberg, Elena
AU - Travis, Marilyn
AU - Cheung, Jeanne
AU - Pflanz, Stefan
AU - Zhang, Rebecca
AU - Singh, Komal P.
AU - Vega, Felix
AU - To, Wayne
AU - Wagner, Janet
AU - O'Farrell, Anne Marie
AU - McClanahan, Terrill
AU - Zurawski, Sandra
AU - Hannum, Charles
AU - Gorman, Daniel
AU - Rennick, Donna M.
AU - Kastelein, Robert A.
AU - De Waal Malefyt, Rene
AU - Moore, Kevin W.
PY - 2002/6/1
Y1 - 2002/6/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.168.11.5699
DO - 10.4049/jimmunol.168.11.5699
M3 - Article
C2 - 12023369
AN - SCOPUS:0036604306
SN - 0022-1767
VL - 168
SP - 5699
EP - 5708
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -