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倾向的NZB和表型正常的NZW小鼠品系的F1杂种已经作为系统性红斑狼疮的小鼠模型进行了研究。NZB和F1杂交小鼠外周血CD 4 ^+ T细胞的自发活化均表现出年龄依赖性，表现为CD 69早期活化标记物阳性的CD 4 + T细胞频率升高。这两种菌株还显示出脾脏中CD 62 L+初始CD 4 + T细胞和/或NTA 260+记忆CD 4 ^+ T细胞频率的年龄依赖性异常降低。我们通过QTL定位和关联规则分析研究了（NZB x NZW）F1 x NZW回交小鼠外周血CD 4 ^+ T细胞异常特征的多基因控制。CD 69 ^+ CD 4 ^+ T细胞频率的异常升高和CD 62 L ^+初始和/或NTA 260 ^+记忆CD 4 ^+ T细胞频率的降低都受到共同的遗传控制，其中MHC与12号染色体上一个迄今未知的位点Sta-1（自发T细胞激活）之间的相互作用起着重要作用。这些基因座的等位基因效应可能使CD 4 ^+ T细胞易于丧失自身耐受性，并导致（NZB x NZW）F1杂种小鼠自身免疫表型的加速。

项目成果

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

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.

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

• DOI: 10.1002/eji.200425267
• 发表时间: 2004-10-01
• 期刊: EUROPEAN JOURNAL OF IMMUNOLOGY
• 影响因子: 5.4
• 作者: Wen, XS;Zhang, DQ;Hirose, S
• 通讯作者: Hirose, S

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.

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