Disease relevance of Il18rap

• Since MRL-Fas(lpr) T cells are characterized by an overexpression of the IL-18 receptor accessory chain, we sought to determine the impact of IL-18 on the progression of lupus nephritis in MRL-Fas(lpr) mice [1].
• These findings have important implications to several conditions in humans, which are associated with long-term defects in IL-1 signaling, such as mutations in the IL-1 receptor accessory protein-like gene, which are involved in a frequent form of X-linked mental retardation [2].

High impact information on Il18rap

• Furthermore, AcPL is required for NK-mediated cytotoxicity induced by in vivo IL-18 stimulation [3].
• In particular, Th1 cells lacking AcPL fail to produce IFN-gamma in response to IL-18 [3].
• Lymphocytes from autoimmune MRL lpr/lpr mice are hyperresponsive to IL-18 and overexpress the IL-18 receptor accessory chain [4].
• IL-18Rbeta expression was significantly increased in response to treatment of mixed glia with bacterial lipopolysaccharide (LPS) in vitro, whereas expression of IL-1Rrp2 and TIGIRR1 was reduced [5].
• Both forms of IL-18Rbeta were expressed in rat cortex, striatum, hypothalamus, hippocampus, and also liver, and were detected in pure cultures of microglia, astrocytes and neurons [6].

Biological context of Il18rap

• Exposure of these cells to IL-12 led not only to up-regulation of IL-18Ralpha expression but also to induction of IL-18R binding sites on both CD4(+) and CD8(+) T cells concomitant with IL-18Rbeta mRNA expression [7].
• IL-18 acts via a receptor complex that closely resembles that of IL-1, consisting of a ligand binding protein, IL-18Ralpha, and an accessory protein, IL-18Rbeta [6].

Anatomical context of Il18rap

• Furthermore, IL-18Rbeta, IL-1Rrp2, but not TIGIRR1 expression, was increased in the brain in vivo in response to peripheral administration of LPS or middle cerebral artery occlusion (MCA) [5].

Other interactions of Il18rap

• In contrast, the expression of the accessory receptor chain IL-18R beta is low in unstimulated +/+ cells but significantly high in lpr/lpr cells [4].

References