Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12.
A novel sequence discovered in a computational screen appears distantly related to the p35 subunit of IL-12. This factor, which we term p19, shows no biological activity by itself; instead, it combines with the p40 subunit of IL-12 to form a novel, biologically active, composite cytokine, which we term IL-23. Activated dendritic cells secrete detectable levels of this complex. IL-23 binds to IL-12R beta 1 but fails to engage IL-12R beta 2; nonetheless, IL-23 activates Stat4 in PHA blast T cells. IL-23 induces strong proliferation of mouse memory (CD4(+)CD45Rb(low)) T cells, a unique activity of IL-23 as IL-12 has no effect on this cell population. Similar to IL-12, human IL-23 stimulates IFN-gamma production and proliferation in PHA blast T cells, as well as in CD45RO (memory) T cells.
Oppmann
B
B
DNAX Research Institute, Palo Alto, CA 94304, USA.
Lesley
R
R
Blom
B
B
Timans
J C
JC
Xu
Y
Y
Hunte
B
B
Vega
F
F
Yu
N
N
Wang
J
J
Singh
K
K
Zonin
F
F
Vaisberg
E
E
Churakova
T
T
Liu
M
M
Gorman
D
D
Wagner
J
J
Zurawski
S
S
Liu
Y
Y
Abrams
J S
JS
Moore
K W
KW
Rennick
D
D
de Waal-Malefyt
R
R
Hannum
C
C
Bazan
J F
JF
Kastelein
R A
RA
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D016208:Databases, Factual; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017421:Sequence Analysis
D016207:Cytokines; C508840:IL23A protein, human; C508841:Il23a protein, mouse; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D018664:Interleukin-12