Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Calcium-Calmodulin-Dependent Protein Kinases / metabolism
-
Cell Differentiation / genetics
-
Cell Differentiation / immunology
-
Cytotoxicity, Immunologic / genetics
-
DNA / immunology
-
Enzyme Activation / genetics
-
Enzyme Activation / immunology
-
Gene Targeting
-
Interleukin-18 / metabolism*
-
Interleukin-18 / physiology
-
Interleukin-18 Receptor alpha Subunit
-
JNK Mitogen-Activated Protein Kinases
-
Killer Cells, Natural / immunology
-
Killer Cells, Natural / pathology
-
Mice
-
Mice, Knockout / genetics
-
Mice, Knockout / immunology*
-
Mitogen-Activated Protein Kinases*
-
NF-kappa B / metabolism
-
Protein Binding / genetics
-
Protein Binding / immunology
-
Proteins / genetics*
-
Proteins / metabolism
-
Receptors, Interleukin / deficiency*
-
Receptors, Interleukin / genetics*
-
Receptors, Interleukin-18
-
Sequence Deletion
-
Spleen / immunology
-
Spleen / pathology
-
Th1 Cells / pathology
Substances
-
Il18r1 protein, mouse
-
Interleukin-18
-
Interleukin-18 Receptor alpha Subunit
-
NF-kappa B
-
Proteins
-
Receptors, Interleukin
-
Receptors, Interleukin-18
-
DNA
-
Calcium-Calmodulin-Dependent Protein Kinases
-
JNK Mitogen-Activated Protein Kinases
-
Mitogen-Activated Protein Kinases