Elucidation of novel immune regulatory mechanism by PILR that belongs to NK cell receptor family.

阐明属于 NK 细胞受体家族的 PILR 的新型免疫调节机制。

• 批准号: 18390151
• 负责人: ARASE Hisashi
• 金额: $ 10.77万
• 依托单位: Osaka 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-18390151/
• 关键词: PILR; CD45; Paired receptors; NK cell; Immune regulation; NK細胞レセプター; 免疫逃避; 単純ヘルペスウィルス

In this study, we have analyzed how PILR, one of NK cell receptor family molecules, is involved in immune system. Especially, we have analyzed how PILR regulates innate immune response and acquired immune response. Furthermore, we have tried to develop a method to regulate allergic diseases and autoimmune diseases by regulating interaction between PILR and PILR ligands. When we have analyzed expression of PILR ligands and function of the ligands, we have found that PILR recognizes CD45 expressed on CD8 T cells. Furthermore, we analyzed the function of the interaction between PILR and CD45, by stimulating T cells with anti-CD3 mAb and PILR-Ig fusion protein. From these analyses, we found that the interaction significantly augment the response of CD8 T cells. Furthermore, PILR expressed on antigen presenting cells significantly augmented the response of T cells. In summary, PILR was revealed to regulate CD8 T cell activation by interacting with CD45 expressed on CD8 T cells. Development of methods to regulate interaction between CD45 and PILR seems to be involved in the development of methods to regulate allergic diseases and autoimmune diseases. Therefore, further analyses of the function of PILR seem to be important to elucidate the mechanism of immune regulation.

本研究分析了NK细胞受体家族分子PILR在免疫系统中的作用。特别分析了PILR对先天性免疫和获得性免疫的调节作用。此外，我们已经尝试开发通过调节PILR和PILR配体之间的相互作用来调节变应性疾病和自身免疫性疾病的方法。当我们分析PILR配体的表达和配体的功能时，我们发现PILR识别在CD 8 T细胞上表达的CD 45。此外，我们还用抗CD 3单克隆抗体和PILR-Ig融合蛋白刺激T细胞，分析了PILR与CD 45相互作用的功能。从这些分析中，我们发现这种相互作用显著增强了CD 8 T细胞的反应。此外，在抗原呈递细胞上表达的PILR显著增强T细胞的应答。总之，PILR通过与CD 8 T细胞上表达的CD 45相互作用来调节CD 8 T细胞活化。调节CD 45和PILR之间相互作用的方法的开发似乎涉及调节过敏性疾病和自身免疫性疾病的方法的开发。因此，深入研究PILR的功能对阐明免疫调节机制具有重要意义。

项目成果

Expression, crystallization and preliminary x-ray diffraction analysis of human paired Ig-like type 2 receptor α (PILR α)

人配对 Ig 样 2 型受体 α (PILR α) 的表达、结晶和初步 X 射线衍射分析

• 发表时间: 2008
• 期刊: J. Immunol. 64
• 作者: Tabata;S.;Kuroki;K;Maita;N.;Wang;J.;Shiratori;I.;Arase;H.;Kohda;D.;Maenaka;K
• 通讯作者: K

An essential role of sialylated O-linked sugar chains in the recognition of mouse CD99 by paired immunolobulin-like type 2 recefor (PILR)

唾液酸化 O 连接糖链在配对免疫球蛋白样 2 型接收器 (PILR) 识别小鼠 CD99 中的重要作用

• 发表时间: 2008
• 期刊: J. Immunol. 180
• 作者: Wang;J.;Shiratori;I.;Satoh;T.;Lanier;L. L.;Arase;H.
• 通讯作者: H.

Expression, crystallization and preliminary X-ray diffraction analysis of human paired Ig-like type 2 receptor alpha (PILRα).

人类配对 Ig 样 2 型受体 α (PILRα) 的表达、结晶和初步 X 射线衍射分析。

• 发表时间: 2008
• 期刊: Ada Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 64
• 作者: Tabata;S.;Kuroki;K.;Maita;N.;Wang;J.;Shiratori;I.;Arase;H.;Kohda;D.;Maenaka;K.
• 通讯作者: K.

KIR3DS1, a Gene Implicated in Resistance to Progression to AIDS, Encodes a DAP12-Associated Receptor Expressed on NK Cells That Triggers NK Cell Activation.

KIR3DS1 是一种与抵抗 AIDS 进展有关的基因，编码在 NK 细胞上表达的 DAP12 相关受体，触发 NK 细胞激活。

• 发表时间: 2007
• 期刊: J. Immunol. 178・2
• 作者: Boyd RL;Takahama Y.;Carr H.William
• 通讯作者: Carr H.William

「研究成果報告書概要(和文)」より

摘自《研究结果报告摘要（日文）》

• 发表时间: 2005
• 作者: Kawauchi;et. al.;Nishimura et al.;Dezawa et al.;Yoshizawa et al.;星野 幹雄;星野 幹雄
• 通讯作者: 星野 幹雄