To investigate the mechanism of autoimmunity and peripheral tolerance in the skin, several transgenic mouse strains expressing membrane-bound ovalbumin (mOVA) as an epidermal self-antigen under the control of keratinocyte-specific promotors, such as keratin 5 and keratin 14, were employed in combination with adoptive transfer of CD8(+) T cells from OT-I mice (OT-I T cells) that recognize an ovalbumin-derived peptide. However, these strains showed bodyweight loss and required additional inflammatory stimuli, such as γ-irradiation and tape-stripping, to induce skin inflammation. In this study, we generated a mouse strain expressing mOVA under the control of human involucrin promoter (involucrin-mOVA mice). In contrast to previous strains, involucrin-mOVA mice spontaneously developed skin inflammation after the transfer of OT-I T cells in the absence of external stimuli without significant bodyweight loss. We focused on the skin infiltration process of OT-I T cells and found that transferred OT-I T cells accumulated around the hair follicles in the early phase of skin inflammation, and in the later phase, the skin inflammation spontaneously resolved despite the remaining OT-I T cells in the skin. Our involucrin-mOVA mice will provide a promising tool to investigate the pathogenesis and the tolerance mechanisms of cytotoxic skin autoimmunity.
A Phenotypic Analysis of Involucrin-Membrane-Bound Ovalbumin Mice after Adoptive Transfer of Ovalbumin-Specific CD8(+) T Cells.
卵清蛋白特异性 CD8(+) T 细胞过继转移后,对膜结合卵清蛋白小鼠进行表型分析
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作者:Nakagawa Yujin, Egawa Gyohei, Miyake Toshiya, Nakajima Saeko, Otsuka Atsushi, Nomura Takashi, Kitoh Akihiko, Dainichi Teruki, Sakabe Jun-Ichi, Shibaki Akihiko, Tokura Yoshiki, Honda Tetsuya, Kabashima Kenji
| 期刊: | JID Innovations | 影响因子: | 0.000 |
| 时间: | 2022 | 起止号: | 2022 Mar 30; 2(5):100127 |
| doi: | 10.1016/j.xjidi.2022.100127 | 靶点: | CD8 |
| 研究方向: | 细胞生物学 | ||
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