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

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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.