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The Regulation of Oral Mucosa Immunity by Immune Co-inhibitory Molecules

免疫共抑制分子对口腔粘膜免疫的调节

基本信息

批准号：
16591884
负责人：
HASHIGUCHI Masaaki
金额：
$ 1.86万
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 (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591884/
关键词：
keratinocyte co-signal molecule mucosal immunity 補助刺激分子

项目摘要

Mucosal tissues including oral cavity are distinguished from the others in the point of immune responses. On the other hand, co-signal molecules are known to function positively or negatively. That is why these molecules are important for the regulation of immune responses. In this research, we aimed to control the unique immune responses of mucosa by a modulation of co-inhibitory molecules on keratinocytes, with a further desire of developing a mucosa vaccination system.Genetically engineered animals are powerful tools for examine in vivo immune responses. We made a construct for the expression of a co-inhibitory molecule, B7-H1 (PD-L1) specifically on keratinocyte under the control of keratin 14 (K14) promoter and using this we established a K14-B7-H1 transgenic mouse. Keratinocytes from this transgenic mouse showed the higher level of B7-H1 but the other cells tested not. On the contact hypersensitivity model with painting DNFB on the belly and ears, K14-B7-H1 transgenic mice showed smaller swellings of ears when a relatively lower dose was administered and showed larger swellings when a relative higher dose was administered. As described previously, B7-H1 is known to be a co-inhibitory molecule. From this points, we had expected the smaller swellings despite of the dosages, but a higher dose induced larger swellings, which suggest that immune responses at mucosa are distinct where B7-H1 is involved. The further investigation is to be accomplished.

包括口腔在内的粘膜组织在免疫反应方面与其他组织不同。另一方面，共信号分子可以发挥积极或消极的作用。这就是为什么这些分子对免疫反应的调节很重要。在这项研究中，我们的目标是通过调节角质形成细胞上的共抑制分子来控制粘膜独特的免疫反应，并进一步开发黏膜免疫系统。我们在角蛋白14(K14)启动子的控制下，构建了共抑制分子B7-H1(PD-L1)在角质形成细胞上的表达载体，并用此构建了K14-B7-H1转基因小鼠。这只转基因小鼠的角质形成细胞显示出更高水平的B7-H1，而其他细胞则没有。在腹部和耳部涂抹DNFB的接触性超敏反应模型上，K14-B7-H1转基因小鼠在相对较低的剂量下表现出较小的耳肿胀，而在相对较高的剂量下表现出较大的耳肿胀。如前所述，B7-H1是已知的共抑制分子。从这一点来看，尽管剂量不同，我们原本预计肿胀会较小，但较高的剂量会导致较大的肿胀，这表明涉及B7-H1的粘膜的免疫反应是明显的。进一步的调查还有待完成。