权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Analysis of the Expression Mechanism of Immunoglobulin E by Interleukin-4

Interleukin-4表达免疫球蛋白E的机制分析

基本信息

批准号：
07670385
负责人：
IZUHARA Kenji
金额：
$ 1.28万
依托单位：
National Institute of Genetics
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670385/
关键词：
Interleukin-4 immunoglobulin E IL-2 Receptor gamma chain IL-4 Receptor Jak3 STAT6 インターロイキン4レセプターインターロイキン13 インターロイキン2レセプターガンマ鎖 XSCID JAK3

项目摘要

(1) Interleukin-4 (IL-4) and IL-13 are functionally similar cytokines. The functional IL-4 receptor (IL-4R) consists of the IL-4Ralpha chain (IL-4Ralpha) and the IL-2Rgamma chain (gamma_c), which is shared by the IL-2, IL-7, IL-9, and IL-15 receptors. The functional IL-13R is thought to involve the IL-4Ralpha, but not gammac. In this study, we have analyzed activation of members of the Janus tyrosine kinase (Jak) family and signal transducers and activators of transcription (STAT) 6 induced by IL-4 and IL-13 in EBV-transformed B cells derived from two patients of X-linked severe combined immunodeficiency (XSCID), who have mutations of the gamma_c gene in the extracellular and intracellular domains. In these B cells, IL-4 failed to induce tyrosine phosphorylation of Jak3 and activation of STAT6, or activation of these molecules was significantly decreased compared with EBV-transformed normal B cells. In contrast, IL-13 activated STAT6 in thses cells as well as normal B cells. However, Jak3 was not activated by IL-13, even in normal B cells. These results clearly indicated that gamma_c is essential for activation of Jak3 and STAT6 in the signal transduction pathway of IL-4 in human B cells, and that IL-13 dose not utilize gamma_c but activates STAT6 through an alternative pathway, which is not impaired in B cells of XSCID patients.

(1)白细胞介素-4（IL-4）和IL-13是功能相似的细胞因子。功能性IL-4受体（IL-4 R）由IL-4 R α链（IL-4 R α）和IL-2 R γ链（γ_c）组成，其由IL-2、IL-7、IL-9和IL-15受体共享。功能性IL-13 R被认为涉及IL-4 R α，但不涉及γ。在这项研究中，我们分析了激活的Janus酪氨酸激酶（Jak）家族成员和信号转导和转录激活因子（STAT）6诱导的IL-4和IL-13在EBV转化的B细胞来自两个患者的X-连锁严重联合免疫缺陷（XSCID），谁有突变的γ_c基因在细胞外和细胞内域。在这些B细胞中，IL-4不能诱导Jak 3的酪氨酸磷酸化和STAT 6的活化，或者与EBV转化的正常B细胞相比，这些分子的活化显著降低。相反，IL-13在这些细胞以及正常B细胞中激活STAT 6。然而，即使在正常B细胞中，Jak 3也不被IL-13激活。这些结果清楚地表明，γ_c是激活人B细胞中IL-4信号转导通路中Jak 3和STAT 6所必需的，并且IL-13不利用γ_c而是通过替代途径激活STAT 6，这在XSCID患者的B细胞中不受损害。