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A mouse model of vitiligo based on endogenous auto-reactive CD8 + T cell targeting skin melanocyte

Vitiligo is the most common human skin depigmenting disorder. It is mediated by endogenous autoreactive CD8 + T cells that destruct skin melanocytes. This disease has an estimated prevalence of 1% of the global population and currently has no cure. Animal models are indispensable tools for understan...

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Autores principales: Chen, Daoming, Xu, Zijian, Cui, Jun, Chen, Ting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Nature Singapore 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9526765/
https://www.ncbi.nlm.nih.gov/pubmed/36182982
http://dx.doi.org/10.1186/s13619-022-00132-9
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author Chen, Daoming
Xu, Zijian
Cui, Jun
Chen, Ting
author_facet Chen, Daoming
Xu, Zijian
Cui, Jun
Chen, Ting
author_sort Chen, Daoming
collection PubMed
description Vitiligo is the most common human skin depigmenting disorder. It is mediated by endogenous autoreactive CD8 + T cells that destruct skin melanocytes. This disease has an estimated prevalence of 1% of the global population and currently has no cure. Animal models are indispensable tools for understanding vitiligo pathogenesis and for developing new therapies. Here, we describe a vitiligo mouse model which recapitulates key clinical features of vitiligo, including epidermis depigmentation, CD8 + T cell infiltration in skin, and melanocyte loss. To activate endogenous autoreactive cytotoxic CD8 + T cells targeting melanocytes, this model relies on transient inoculation of B16F10 melanoma cells and depletion of CD4 + regulatory T cells. At cellular level, epidermal CD8 + T cell infiltration and melanocyte loss start as early as Day 19 after treatment. Visually apparent epidermis depigmentation occurs 2 months later. This protocol can efficiently induce vitiligo in any C57BL/6 background mouse strain, using only commercially available reagents. This enables researchers to carry out in-depth in vivo vitiligo studies utilizing mouse genetics tools, and provides a powerful platform for drug discovery.
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spelling pubmed-95267652022-10-14 A mouse model of vitiligo based on endogenous auto-reactive CD8 + T cell targeting skin melanocyte Chen, Daoming Xu, Zijian Cui, Jun Chen, Ting Cell Regen Methodology Vitiligo is the most common human skin depigmenting disorder. It is mediated by endogenous autoreactive CD8 + T cells that destruct skin melanocytes. This disease has an estimated prevalence of 1% of the global population and currently has no cure. Animal models are indispensable tools for understanding vitiligo pathogenesis and for developing new therapies. Here, we describe a vitiligo mouse model which recapitulates key clinical features of vitiligo, including epidermis depigmentation, CD8 + T cell infiltration in skin, and melanocyte loss. To activate endogenous autoreactive cytotoxic CD8 + T cells targeting melanocytes, this model relies on transient inoculation of B16F10 melanoma cells and depletion of CD4 + regulatory T cells. At cellular level, epidermal CD8 + T cell infiltration and melanocyte loss start as early as Day 19 after treatment. Visually apparent epidermis depigmentation occurs 2 months later. This protocol can efficiently induce vitiligo in any C57BL/6 background mouse strain, using only commercially available reagents. This enables researchers to carry out in-depth in vivo vitiligo studies utilizing mouse genetics tools, and provides a powerful platform for drug discovery. Springer Nature Singapore 2022-10-02 /pmc/articles/PMC9526765/ /pubmed/36182982 http://dx.doi.org/10.1186/s13619-022-00132-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Methodology
Chen, Daoming
Xu, Zijian
Cui, Jun
Chen, Ting
A mouse model of vitiligo based on endogenous auto-reactive CD8 + T cell targeting skin melanocyte
title A mouse model of vitiligo based on endogenous auto-reactive CD8 + T cell targeting skin melanocyte
title_full A mouse model of vitiligo based on endogenous auto-reactive CD8 + T cell targeting skin melanocyte
title_fullStr A mouse model of vitiligo based on endogenous auto-reactive CD8 + T cell targeting skin melanocyte
title_full_unstemmed A mouse model of vitiligo based on endogenous auto-reactive CD8 + T cell targeting skin melanocyte
title_short A mouse model of vitiligo based on endogenous auto-reactive CD8 + T cell targeting skin melanocyte
title_sort mouse model of vitiligo based on endogenous auto-reactive cd8 + t cell targeting skin melanocyte
topic Methodology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9526765/
https://www.ncbi.nlm.nih.gov/pubmed/36182982
http://dx.doi.org/10.1186/s13619-022-00132-9
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