Mechanism of immune-surveillance and immune-regulation by paired receptors

配对受体的免疫监视和免疫调节机制

• 批准号: 16043210
• 负责人: ARASE Hisashi
• 金额: $ 25.34万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16043210/
• 关键词: Paired receptor; PILR; Immune surveillance; Immune regulation; Basophil; T cell; Dendritic cells; NK細胞レセプター; CD200; NK細胞; ヘルパーT細胞

Paired receptors that consist of activating and inhibitory receptors seem to have been evolved with pathogens such as viruses. However, further analyses revealed that some of paired receptors recognize specific self-antigens. Especially, PILR that is mainly expressed on NK cells and dendritic cells recognizes specific ligand expressed on Th2 cells. In the present study, we further screened the ligand for PILR and analyzed the function of PILR in immune surveillance. We found that the ligand for PILR strongly activate NK cells and dendritic cells (Shiratori et aL J. Exp. Med. 2004). Furthermore, we found that regulatory molecules expressed on T cells are ligand for PILR (Patent : PCT/JP2007/053558). In addition, we found that certain glycan is involved in the ligand recognition by PILR. In order to analyze the function of PILR in vivo, we successfully established PILR-deficient mice. PILR-deficient mice will provide further information how paired receptors are involved in immune surveillance. On the other hand, we found that inhibitory CD200 receptor is expressed on basophil and regulates the activation of basophil (Shiratori et at J. Immunoi 2005). Because basophil is known to be involved in allergic response, our study suggested a new target molecule for the regulation of allergic diseases.

包括激活和抑制性受体组成的成对受体似乎已经通过病原体（例如病毒）演化。但是，进一步的分析表明，一些配对受体识别特定的自我抗原。特别是，主要在NK细胞和树突状细胞上表达的PILR识别在Th2细胞上表达的特定配体。在本研究中，我们进一步筛选了PILR的配体，并分析了PILR在免疫监视中的功能。我们发现PILR的配体强烈激活NK细胞和树突状细胞（Shiratori等人J.Exp。Med。2004）。此外，我们发现在T细胞上表达的调节分子是PILR的配体（专利：PCT/JP2007/053558）。此外，我们发现某些聚糖参与PILR的配体识别。为了分析PILR在体内的功能，我们成功地建立了PILR缺陷型小鼠。缺乏PILR的小鼠将提供进一步的信息，如何参与免疫监测。另一方面，我们发现抑制性CD200受体在嗜碱性粒细胞上表达并调节嗜碱性粒细胞的激活（Shiratori et at J. Immunoi 2005）。由于已知嗜碱性粒细胞参与过敏反应，因此我们的研究提出了一种用于调节过敏性疾病的新靶分子。

项目成果

PILRαと結合するポリペプチド、およびそれをコードするポリヌクレオチド、並びにその利用

与PILRα结合的多肽、编码其的多核苷酸及其用途

• 发表时间: 2006

IgE-mediated activation of NK cells through FcyRIII

IgE 通过 FcyRIII 介导的 NK 细胞激活

• 发表时间: 2003
• 期刊: J. Immuno. 170
• 作者: Arase;N.
• 通讯作者: N.

Involvement of FcR T in signal transduction of osteoclast-associated receptor (OSCAR).

FcR T 参与破骨细胞相关受体 (OSCAR) 的信号转导。

• 发表时间: 2004
• 期刊: Int. Immunol. 16
• 作者: Ishikawa;S.
• 通讯作者: S.

IgE-mediated activation of NK cells through FcγRIII

• DOI: 10.4049/jimmunol.170.6.3054
• 发表时间: 2003-03-15
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Arase, N;Arase, H;Saito, T
• 通讯作者: Saito, T

NKG2D-mediated natural killer cell protection against cytomegalovirus is impaired by viral gp40 modulation of retinoic acid early inducible 1 gene molecules.

• DOI: 10.1084/jem.20021973
• 发表时间: 2003-05-19
• 期刊: The Journal of experimental medicine
• 作者: Lodoen M;Ogasawara K;Hamerman JA;Arase H;Houchins JP;Mocarski ES;Lanier LL
• 通讯作者: Lanier LL