Genetic control of the defective immune tolerance in systemic lupus erythematosus-prone New Zealand Black mice.

对易患系统性红斑狼疮的新西兰黑小鼠免疫耐受缺陷的遗传控制。

• 批准号: 15590282
• 负责人: NISHIMURA Hiroyuki
• 金额: $ 1.98万
• 依托单位: TOIN HUMAN SCIENCE AND TECHNOLOGY CENTER, TOIN UNIVERSITY OF YOKOHAMA
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590282/
• 关键词: immune tolerance; autoimmune disease; SLE; systemic lupus erythematosus; NZB mice; disease susceptibility gene; genetic linkage study; Fc receptor; 全身性自己免疫疾患; 遺伝支配; C57BL; 6系マウス; 免疫グロブリン; ポリエチレングリコール; 連鎖解析; 疾患感受性; ゲノムマッピング; New Zealand系マウ

The F1 hybrid of autoimmune hemolytic anemia-prone NZB and phenotypically normal NZW strains of mice has been studied as a murine model of systemic lupus erythematosus. Both NZB and F1 hybrid mice show age-dependent spontaneous activation of peripheral CD4^+ T cells as reflected by the elevated frequencies of CD4+ T cells positive for CD69 early activation marker. Both strains also show age-dependent abnormal decrease of the frequencies of CD62L+ naive CD4+ T cells and/or NTA260+ memory CD4^+ T cells in the spleen. We studied the multigenic control of these abnormal features of peripheral CD4^+ T cells in (NZB x NZW) F1 x NZW backcross mice by QTL mapping and by association rule analysis. The abnormally elevated frequencies of CD69^+CD4^+ T cells and decreased frequencies of CD62L^+ naive and/or NTA260^+ memory CD4^+ T cells were under the common genetic control, in which the interaction between MHC and a hitherto unknown locus, designated Sta-1 (spontaneous T-cell activation) on chromosome 12, plays a major role. The allelic effects of these loci likely predispose CD4^+ T cells to the loss of self-tolerance, and are responsible for the accelerated autoimmune phenotypes of (NZB x NZW) F1 hybrid m

自身免疫性溶血性贫血的NZB和表型正常的NZW菌株的F1杂种已被研究为全身性红斑狼疮的鼠模型。 NZB和F1杂交小鼠均显示出周围CD4^+ T细胞的年龄依赖性自发激活，这是由CD69早期激活标记阳性的CD4+ T细胞的升高频率反映的。这两种菌株还显示了CD62L+ NAIVE CD4+ T细胞的频率和/或NTA260+记忆CD4^+ T细胞的频率的异常降低。我们通过QTL映射和通过关联规则分析研究了（NZB X NZW）F1 X NZW反向交叉小鼠（NZB X NZW）中外周三^+ T细胞的这些异常特征的多基因控制。 The abnormally elevated frequencies of CD69^+CD4^+ T cells and decreased frequencies of CD62L^+ naive and/or NTA260^+ memory CD4^+ T cells were under the common genetic control, in which the interaction between MHC and a hitherto unknown locus, designated Sta-1 (spontaneous T-cell activation) on chromosome 12, plays a major role.这些基因座的等位基因效应可能使CD4^+ T细胞易于自我耐受，并负责（NZB x NZW）F1混合M的加速自身免疫表型

项目成果

Transgene-mediated hyper-expression of IL-5 inhibits autoimmune disease but increases the risk of B cell chronic lymohocytic leukemia in a model of murine lupus

转基因介导的 IL-5 过度表达可抑制自身免疫性疾病，但会增加小鼠狼疮模型中 B 细胞慢性淋巴细胞白血病的风险

• 发表时间: 2004
• 期刊: Eur.J.Immunol. 34
• 作者: 西村裕之;広瀬幸子;Wen X et al.;Li N et al.;Zhang D. et al.;Wen X.et al.
• 通讯作者: Wen X.et al.

Dissection of the role of MHC class II A and E genes in autoimmune susceptibility in murine lupus models with intragenic recombination.

剖析 MHC II 类 A 类和 E 类基因在具有基因内重组的小鼠狼疮模型中自身免疫易感性中的作用。

• 发表时间: 2004
• 期刊: Proc Natl Acad Sci USA. 101
• 作者: Zhang D;Fujio K;Jiang Y;et al.
• 通讯作者: et al.

SLE遺伝子

系统性红斑狼疮基因

• 发表时间: 2005
• 期刊: 「免疫2005」Molecular Medicine 臨時増刊号 41
• 作者: 西村裕之;広瀬幸子
• 通讯作者: 広瀬幸子

Correlation of aggression with serum IgM level in autoimmune-prone NZB mice.

具有自身免疫倾向的 NZB 小鼠的攻击行为与血清 IgM 水平的相关性。

• 发表时间: 2005
• 期刊: Dev. Brain Res. 159
• 作者: Nakamura K;Nishimura H;Hirose S et al.
• 通讯作者: Hirose S et al.

SLE感受性遺伝子

系统性红斑狼疮易感基因

• 发表时间: 2005
• 期刊: 免疫2005(Molecular medicine) 41 臨時増刊号
• 作者: Hiroyuki Kato;Shiori Tamamizu-Kato;Futoshi Shibasaki;Okamoto H et al.;Nakamura K et al.;Ikeda K. et al.;西村裕之 他
• 通讯作者: 西村裕之 他