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A Phenotypic Analysis of Involucrin–Membrane-Bound Ovalbumin Mice after Adoptive Transfer of Ovalbumin-Specific CD8(+) T Cells

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 combina...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9460514/
https://www.ncbi.nlm.nih.gov/pubmed/36090298
http://dx.doi.org/10.1016/j.xjidi.2022.100127
Descripción
Sumario: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.