Cutting edge: generation of IL-18 receptor-deficient mice: evidence for IL-1 receptor-related protein as an essential IL-18 binding receptor.
IL-18 is a proinflammatory cytokine that plays an important role in NK cell activation and Th1 cell response. Recently IL-1R-related protein (IL-1Rrp) has been cloned as the receptor for IL-18. However, the functional role of IL-1Rrp is still controversial due to its low affinity to IL-18 as well as the possibility of the presence of another high-affinity binding receptor. In the present study, we have generated and characterized IL-1Rrp-deficient mice. The binding of murine rIL-18 was not detected in Th1-developing splenic CD4+ T cells isolated from IL-1Rrp-deficient mice. The activation of NF-kappa B or c-Jun N-terminal kinase were also not observed in the Th1 cells. NK cells from IL-1Rrp-deficient mice had defects in cytolytic activity and IFN-gamma production in response to IL-18. Th1 cell development was also impaired in IL-1Rrp-deficient mice. These data demonstrate that IL-1Rrp is a ligand-binding receptor that is essential for IL-18-mediated signaling events.
Hoshino
K
K
Department of Appropriate Technology Development, Research Institute, International Medical Center of Japan, Tokyo, Japan.
Tsutsui
H
H
Kawai
T
T
Takeda
K
K
Nakanishi
K
K
Takeda
Y
Y
Akira
S
S
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004247:DNA / Q000276:immunology; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D018390:Gene Targeting; D020382:Interleukin-18 / Q000378:metabolism* / Q000502:physiology; D053727:Interleukin-18 Receptor alpha Subunit; D048031:JNK Mitogen-Activated Protein Kinases; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics / Q000276:immunology*; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D018123:Receptors, Interleukin / Q000172:deficiency* / Q000235:genetics*; D053724:Receptors, Interleukin-18; D017384:Sequence Deletion; D013154:Spleen / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000473:pathology
C508573:Il18r1 protein, mouse; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D016328:NF-kappa B; D011506:Proteins; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D004247:DNA; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases