Analysis of Mucosal Immunity by the Fc receptor for IgA and IgM

IgA 和 IgM Fc 受体的粘膜免疫分析

• 批准号: 14207024
• 负责人: SHIBUYA Akira
• 金额: $ 27.62万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14207024/
• 关键词: Fcα; μ receptor; IgA; IgM; Paneth cell; Antibacteria; Fc receptor; 自然免疫; 獲得免疫; 免疫グロブリン; 生体防御

We previously identified an Fc receptor for IgA and IgM (Fcα/μ receptor), which is expressed on antigen presenting cells. We found that the Fcα/μ receptor mediated endocytosis of IgM immune complex with antigen, such as staphylococcus aureus, suggesting an important mechanisms of pathogen eradication by IgM. The present study aims to clarify a role of the Fcα/μ receptor in mucosal immunity. We have identified several isoforms of the soluble Fcα/μ receptor expressed on intestinal Paneth cells and epithelial cells of urinary tract. We found that the extracellular domain of the isoforms may have antimicrobial activity against E.coli. Furthermore, we observed that mice deficient in the Fcα/μ receptor gene exhibited high IgA concentration in both serum and fecus and the presence of many IgA producing cells in lamina proplia.We also observed that the Fcα/μ receptor was strongly expressed on the area of germinal center. Immunohistochemical study revealed that FDC substantially expressed the Fcα/μ receptor in germinal center. These results suggest that the Fcα/μ receptor regulates IgA production in peyel's patches and/or intestinal flora by the soluble Fcα/μ receptor secreted from Paneth cells. Furthermore, we studied the mucosal immune responses by antigen challenge in mice deficient in the the Fcα/μreceptor gene.

我们先前鉴定了伊加和IgM的Fc受体（Fcα/μ受体），其在抗原呈递细胞上表达。我们发现Fcα/μ受体介导IgM免疫复合物与抗原的内吞作用，如金黄色葡萄球菌，提示IgM清除病原体的重要机制。本研究旨在阐明Fcα/μ受体在粘膜免疫中的作用。我们已经鉴定了可溶性Fcα/μ受体的几种亚型，它们表达于肠Paneth细胞和泌尿道上皮细胞上。我们发现，胞外结构域的异构体可能对大肠杆菌具有抗菌活性。此外，我们还观察到Fcα/μ受体基因缺陷小鼠血清和粪便中伊加浓度均升高，前板中存在大量伊加产生细胞，并观察到Fcα/μ受体在生发中心区域有强表达。免疫组化结果显示，FDC在生发中心表达Fcα/μ受体。这些结果表明Fcα/μ受体通过潘氏细胞分泌的可溶性Fcα/μ受体调节派伊尔斑和/或肠道植物群中伊加的产生。此外，我们还研究了Fcα/μ受体基因缺陷小鼠的粘膜免疫应答。

项目成果

Successful gene transfer into human CD4 positive T cells mediated by lentiviral vectors.

由慢病毒载体介导成功地将基因转移到人类 CD4 阳性 T 细胞中。

• 发表时间: 2004
• 期刊: Immunology 12
• 作者: Shibuya K;et al.
• 通讯作者: et al.

Kojima H., Shibuya A.et al.: "CD226 mediates platelet and megakaryocytic cell adhesion to vascular endothelial cells"J.Biol.Chem.. 278・367. 48-53 (2003)

小岛H.、涩谷A.等：“CD226介导血小板和巨核细胞与血管内皮细胞的粘附”J.Biol.Chem.. 278・367(2003)。

Requirement of the serine at residue 329 for lipid raft recruitmet of DNAM-1 (CD226)

DNAM-1 (CD226) 脂筏招募需要残基 329 处的丝氨酸

• 发表时间: 2005
• 期刊: Int Immunol 17
• 作者: Shirakawa J;Shibuya K;Shibuya;A.
• 通讯作者: A.

Requirement of the tyrosines at residues 258 and 270 of MAIR-1 in inhibitory effect on degranulation from basophilic leukemia RBL-2H3.

MAIR-1 残基 258 和 270 处的酪氨酸对嗜碱性白血病 RBL-2H3 脱粒的抑制作用的需要。

• 发表时间: 2005
• 期刊: International Immunology 17
• 作者: Suto A;Nakajima H;Takatori H;Tokumasa N;Suzuki K;Iwamoto I;Shirakawa J et al.;Shibuya A et al.;Okoshi Y et al.
• 通讯作者: Okoshi Y et al.

Treatment with alpha-galactosylceramide attenuates the development of bleomycin-induced pulmonary fibrosis.

• 发表时间: 2004
• 期刊: Journal of immunology
• 影响因子: 4.4
• 作者: Toru Kimura;Yukio Ishii;Y. Morishima;A. Shibuya;K. Shibuya;M. Taniguchi;M. Mochizuki;A. Hegab;T. Sakamoto;A. Nomura;K. Sekizawa