Pathogenesis of SLE: Linkage Analysis of Critical Signaling Pathways

SLE 发病机制：关键信号通路的连锁分析

• 批准号: 23591450
• 负责人: NISHIMURA Hiroyuki
• 金额: $ 3.24万
• 依托单位: 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: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591450/
• 关键词: 全身性エリテマトーデス; SLE; 全身性自己免疫疾患; 疾患感受性遺伝子; 遺伝連鎖解析; QTL解析; 多因子疾患; 免疫寛容; Fcgr2b; FcgRIIB; MHC class II; 自己免疫疾患; NZB mice; NZW mice; 自己免役疾患

In contrast to normal mice, autoimmune-prone New Zealand Black (NZB) mice are defective in susceptibility to tolerance induced by deaggregated bovine gamma globulin (DBGG). Susceptibility loci for this defect were examined by genome-wide analysis using F2 intercross of non-autoimmune C57BL/6 (B6) and NZB mice. One NZB locus on the telomeric chromosome 1, designated Dit (Defective immune tolerance)-1, showed a highly significant linkage. This locus overlapped with t a locus coding for polymorphic Fcgr2b and Slam family genes. The similar defective tolerance was observed in Fcgr2b-deficient mice with autoimmune-type Slam family genes, but not in Fcgr2b-deficient mice with normal C57BL/6-type Slam family genes indicating that epistatic interaction of both polymorphic genes is involved. Thus, this epistatic interaction is likely playing a pivotal role in the genetic predisposition to autoimmunity in NZB and related autoimmune-prone strains inclusing SLE model (NZB x NZW) F1 mice.

与正常小鼠相比，自身免疫性易免疫的新西兰黑色（NZB）小鼠在脱致牛伽玛球蛋白（DBGG）诱导的耐受性易感性上有缺陷。使用非自动免疫性C57BL/6（B6）和NZB小鼠的F2间交叉通过基因组间分析检查了该缺陷的易感基因座。端粒染色体上的一个NZB基因座，指定的DIT（免疫耐受性有缺陷）-1显示出非常显着的连锁。该基因座与T基因座重叠，编码为多态性FCGR2B和大满贯家族基因。 在具有自身免疫型大型家族基因的FCGR2B缺陷小鼠中观察到了相似的耐受性，但在正常C57BL/6型大型家族基因的FCGR2B缺陷小鼠中未观察到，这表明两种多态性基因都涉及这两种多态性基因。因此，这种上皮的相互作用可能在NZB的自身免疫性及其相关的自身免疫性 - 易免疫性菌株（NZB X NZW）F1小鼠中起关键作用。

项目成果

ポリエチレングリコール修飾抗原によって誘導されるTh細胞免疫寛容の機序・Mechanism of Th-cell tolerance induced with tolerogenic protein antigen conjugated with polyethylene glycol.

聚乙二醇缀合的耐受蛋白抗原诱导 Th 细胞耐受的机制。

• 发表时间: 2011
• 作者: 藤原龍;尾畑賢臣;藤井琢磨;大辻希樹;小寺洋;広瀬幸子;西村裕之
• 通讯作者: 西村裕之

The role of SLAM-signal in SLE.

SLAM 信号在 SLE 中的作用。

• 发表时间: 2012
• 作者: Lin Q;Tsurui H;Nishikawa K;Okazaki H;Ohtsuji M;Nishimura H;Ono M;Shirai T;Hirose S.
• 通讯作者: Hirose S.