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.

我们之前鉴定了 IgA 和 IgM 的 Fc 受体（Fcα/μ 受体），它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（例如金黄色葡萄球菌）的内吞作用，这表明 IgM 消灭病原体的重要机制。本研究旨在阐明 Fcα/μ 受体在粘膜免疫中的作用。我们已经鉴定出在肠潘氏细胞和泌尿道上皮细胞上表达的可溶性 Fcα/μ 受体的几种亚型。我们发现同工型的胞外结构域可能对大肠杆菌具有抗菌活性。此外，我们观察到Fcα/μ受体基因缺陷的小鼠在血清和粪便中表现出高IgA浓度，并且在固有层中存在许多产生IgA的细胞。我们还观察到Fcα/μ受体在生发中心区域强烈表达。免疫组化研究表明，FDC在生发中心大量表达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受体调节培伊尔氏斑和/或肠道菌群中IgA的产生。此外，我们研究了 Fcα/μ 受体基因缺陷小鼠的抗原攻击引起的粘膜免疫反应。

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