Hoshino K, Tsutsui H, Kawai T, Takeda K, Nakanishi K, Takeda Y, Akira S
Department of Appropriate Technology Development, Research Institute, International Medical Center of Japan, Tokyo, Japan.
J Immunol. 1999 May 1;162(9):5041-4.
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.
白细胞介素-18（IL-18）是一种促炎细胞因子，在自然杀伤（NK）细胞活化和辅助性T细胞1（Th1细胞）应答中发挥重要作用。最近，白细胞介素-1受体相关蛋白（IL-1Rrp）已被克隆为IL-18的受体。然而，由于其对IL-18的亲和力较低以及可能存在另一种高亲和力结合受体，IL-1Rrp的功能作用仍存在争议。在本研究中，我们构建并鉴定了IL-1Rrp基因敲除小鼠。在从IL-1Rrp基因敲除小鼠分离的正在发育为Th1细胞的脾脏CD4 + T细胞中，未检测到鼠源重组IL-18的结合。在Th1细胞中也未观察到核因子κB（NF-κB）或c-Jun氨基末端激酶的激活。IL-1Rrp基因敲除小鼠的NK细胞在对IL-18的细胞溶解活性和γ干扰素产生方面存在缺陷。IL-1Rrp基因敲除小鼠的Th1细胞发育也受到损害。这些数据表明，IL-1Rrp是一种配体结合受体，对IL-18介导的信号转导事件至关重要。
