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

包括口腔在内的粘液组织在免疫应答方面与其他组织不同。另一方面，已知共信号分子起正或负作用。这就是为什么这些分子对免疫反应的调节很重要。在本研究中，我们的目的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，并进一步发展粘膜疫苗接种系统。我们构建了一种在角蛋白14（K14）启动子控制下在角质形成细胞上特异性表达共抑制分子B7-H1（PD-L1）的构建体，并使用该构建体建立了K14-B7-H1转基因小鼠。来自该转基因小鼠的角质形成细胞显示出较高水平的B7-H1，但测试的其他细胞没有。在腹部和耳朵涂DNFB的接触性超敏反应模型中，K14-B7-H1转基因小鼠在给予相对较低剂量时耳朵肿胀较小，而在给予相对较高剂量时耳朵肿胀较大。如前所述，已知B7-H1是共抑制分子。从这一点来看，尽管剂量不同，但我们预期的是较小的血清学应答，但较高的剂量诱导较大的血清学应答，这表明在涉及B7-H1的粘膜处的免疫应答是不同的。进一步的调查有待完成。

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.