Immunogenetic analysis of the resistance to infectious diseases

传染病抵抗力的免疫遗传学分析

• 批准号: 18406019
• 负责人: TSUBATA Takeshi
• 金额: $ 6.89万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18406019/
• 关键词: SARS; polymorphism; CD22; CD72; B lymphocyte; infectious diseases; alternative splicing; ER stress; CD7 2; 多型; ハプロタイプ

Both CD22 and CD72 are B lymphocyte membrane molecules that negatively regulate signaling thorough B cell antigen receptor. Both CD22 and CD72 genes are polymorphic. To elucidate whether polymorphisms of these genes are associated with resistance to acute infection, we examined haplotypes of both CD22 and CD72 in SARS patients in China and individuals who were close contact with SARS patients but did not develop SARS. A CD72 haplotype was tend to be increased in patients with severe symptoms although the increase was not significant because of the limited sample numbers. Next, we examined the functional difference of different CD72 haplotypes. The human CD72 gene generates two distinct splicing isoforms, i.e., full length CD72 and CD72 lacking exon 8 (CD72 Δ ex8). We demonstrated that the level of CD72 Δ ex8 but not full length CD72 depends on CD72 haoplotypes. Moreover, CD72 Δ ex8 is accumulated in the endoplastic reticulum (ER), and augments ER stress and apoptosis mediated by ER stress. These results indicate that CD72 polymorphism regulates expression of CD72 Δ ex8 that regulates B lymphocyte apoptosis mediated by ER stress, thereby regulating infection immunity.

CD22 和 CD72 都是 B 淋巴细胞膜分子，可通过 B 细胞抗原受体负向调节信号传导。为了阐明这些基因的多态性是否与急性感染抵抗力相关，我们检查了 CD22 和 CD72 的单倍型。在中国的 SARS 患者以及与 SARS 患者密切接触但未患 SARS 的个体中，CD72 单倍型在症状严重的患者中往往会增加。由于样本数量有限，因此并不显着。 接下来，我们检查了不同 CD72 单倍型的功能差异，我们证明了人类 CD72 基因产生两种不同的剪接异构体，即全长 CD72 和缺乏外显子 8 的 CD72。 CD72 Δ ex8 的水平而非全长 CD72 取决于 CD72 单倍型。此外，CD72 Δ ex8 累积在这些结果表明，CD72 多态性调节 CD72 Δ ex8 的表达，而 CD72 Δ ex8 调节 ER 应激介导的 B 淋巴细胞凋亡，从而调节感染免疫。

项目成果

T Siglec-2 is a key molecule for immune response.

T Siglec-2 是免疫反应的关键分子。

• 发表时间: 2008
• 期刊: In Experimental Glycoscience, Glycobiology (ed by N. Taniguchi, A. Suzuki, Y. Ito, H. Narimatsu, T. Kawasaki and S. Hase) (Springer.)
• 作者: Tsubata;T
• 通讯作者: T

膜型レクチン分子における液性免疫応答の制御

膜型凝集素分子对体液免疫反应的调节

• 发表时间: 2007
• 作者: 人見祐基;安達貴弘;岩井佳子;土屋尚之;本田善一郎;徳永勝士;鍔田武志;鍔田武志;鍔田武志
• 通讯作者: 鍔田武志

B細胞共受容体CD22とCD72の機能と糖鎖リガンドAnnual Review免疫2008

B 细胞辅助受体 CD22 和 CD72 以及碳水化合物配体的功能 免疫学年度评论 2008

• 发表时间: 2007
• 作者: Tsubata;T;鍔田武志
• 通讯作者: 鍔田武志

CD22阻害化合物の構造活性相関

CD22抑制化合物的构效关系

• 发表时间: 2008
• 作者: 玉中大智;Hajjaj H. M. Abdu-Allah;Jie Yu;Lu Zhuoyuan;Magesh Sadagopan;安達貴弘;鍔田武志;Soerge Kelm;石田秀治;木曾眞
• 通讯作者: 木曾眞

Membrane-bound lectins and humoral immunity

膜结合凝集素和体液免疫

• 发表时间: 2009
• 作者: Tsubata;T.
• 通讯作者: T.