The Formation of Melanocyte Apoptotic Bodies in Vitiligo and the Relocation of Vitiligo Autoantigens under Oxidative Stress

Background. Oxidative stress has a vital role in the early stages of vitiligo. Autoantigens released from apoptotic melanocytes (MC) under oxidative stress are involved in the presentation and recognition of antigens. However, the transport of autoantigens to the cell surface and their release to th...

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Autores principales:	Jun Tian, Yaojun Wang, Ming Ding, Yue Zhang, Jiaoni Chi, Tao Wang, Bin Jiao, Zhe Jian, Xiuli Yi, Ye Huang, Ling Liu, Kai Li, Jiaxi Chen, Gang Wang, Tianwen Gao, Chunying Li, Qiang Li
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/cdf2cf55051a471b9e0ef7fed3a684e6
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spelling	oai:doaj.org-article:cdf2cf55051a471b9e0ef7fed3a684e62021-11-08T02:36:16ZThe Formation of Melanocyte Apoptotic Bodies in Vitiligo and the Relocation of Vitiligo Autoantigens under Oxidative Stress1942-099410.1155/2021/7617839https://doaj.org/article/cdf2cf55051a471b9e0ef7fed3a684e62021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/7617839https://doaj.org/toc/1942-0994Background. Oxidative stress has a vital role in the early stages of vitiligo. Autoantigens released from apoptotic melanocytes (MC) under oxidative stress are involved in the presentation and recognition of antigens. However, the transport of autoantigens to the cell surface and their release to the extracellular environment are still unclear. Apoptotic bodies (ABs) have always been considered as a key source of immunomodulators and autoantigens. Yet, the role of ABs in the immune mechanism of vitiligo is still unknown. Purpose. To explore whether MC’s autoantigens translocate into ABs during oxidative stress-induced apoptosis and study the molecular mechanisms underlying autoantigen migration and AB formation. Methods. PIG3V (an immortalized human vitiligo melanocyte cell line) were treated with H2O2, and ABs were separated. Transmission electron microscopy, flow cytometry, Western blot, mass spectrometry, and other methods were used to determine the relocation of specific antigens in PIG3V cells to ABs. After pretreatment with specific inhibitors (Rho kinase (Y-27632), myosin light chain kinase (MLCK, ML-9), pan-caspase (zVAD-FMK), and JNK (SP600125)), the pathway of autoantigen translocation into ABs and the formation of apoptotic bodies were determined. Results. When treated with 0.8 mM H2O2, ABs were released from these cells. Autoantigens such as tyrosinase-related protein 1 (TYRP-1) and cleavage nuclear membrane antigen Lamin A/C (Asp230) were concentrated in ABs. The expression of autoantigens and the formation of ABs increased in a time- and dose-dependent manner after treatment with H2O2, while the application of specific inhibitors inhibited the formation of apoptotic bodies, i.e., the expression of antigens. Conclusion. Vitiligo autoantigens translocate into ABs in the process of apoptosis induced by oxidative stress. The cytoskeletal protein activation pathway and the JNK-related apoptosis pathway are involved in the transport of autoantigens and the formation of ABs. ABs may be the key bridge between MC cell apoptosis and cellular immunity.Jun TianYaojun WangMing DingYue ZhangJiaoni ChiTao WangBin JiaoZhe JianXiuli YiYe HuangLing LiuKai LiJiaxi ChenGang WangTianwen GaoChunying LiQiang LiHindawi LimitedarticleCytologyQH573-671ENOxidative Medicine and Cellular Longevity, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Jun Tian Yaojun Wang Ming Ding Yue Zhang Jiaoni Chi Tao Wang Bin Jiao Zhe Jian Xiuli Yi Ye Huang Ling Liu Kai Li Jiaxi Chen Gang Wang Tianwen Gao Chunying Li Qiang Li The Formation of Melanocyte Apoptotic Bodies in Vitiligo and the Relocation of Vitiligo Autoantigens under Oxidative Stress
description	Background. Oxidative stress has a vital role in the early stages of vitiligo. Autoantigens released from apoptotic melanocytes (MC) under oxidative stress are involved in the presentation and recognition of antigens. However, the transport of autoantigens to the cell surface and their release to the extracellular environment are still unclear. Apoptotic bodies (ABs) have always been considered as a key source of immunomodulators and autoantigens. Yet, the role of ABs in the immune mechanism of vitiligo is still unknown. Purpose. To explore whether MC’s autoantigens translocate into ABs during oxidative stress-induced apoptosis and study the molecular mechanisms underlying autoantigen migration and AB formation. Methods. PIG3V (an immortalized human vitiligo melanocyte cell line) were treated with H2O2, and ABs were separated. Transmission electron microscopy, flow cytometry, Western blot, mass spectrometry, and other methods were used to determine the relocation of specific antigens in PIG3V cells to ABs. After pretreatment with specific inhibitors (Rho kinase (Y-27632), myosin light chain kinase (MLCK, ML-9), pan-caspase (zVAD-FMK), and JNK (SP600125)), the pathway of autoantigen translocation into ABs and the formation of apoptotic bodies were determined. Results. When treated with 0.8 mM H2O2, ABs were released from these cells. Autoantigens such as tyrosinase-related protein 1 (TYRP-1) and cleavage nuclear membrane antigen Lamin A/C (Asp230) were concentrated in ABs. The expression of autoantigens and the formation of ABs increased in a time- and dose-dependent manner after treatment with H2O2, while the application of specific inhibitors inhibited the formation of apoptotic bodies, i.e., the expression of antigens. Conclusion. Vitiligo autoantigens translocate into ABs in the process of apoptosis induced by oxidative stress. The cytoskeletal protein activation pathway and the JNK-related apoptosis pathway are involved in the transport of autoantigens and the formation of ABs. ABs may be the key bridge between MC cell apoptosis and cellular immunity.
format	article
author	Jun Tian Yaojun Wang Ming Ding Yue Zhang Jiaoni Chi Tao Wang Bin Jiao Zhe Jian Xiuli Yi Ye Huang Ling Liu Kai Li Jiaxi Chen Gang Wang Tianwen Gao Chunying Li Qiang Li
author_facet	Jun Tian Yaojun Wang Ming Ding Yue Zhang Jiaoni Chi Tao Wang Bin Jiao Zhe Jian Xiuli Yi Ye Huang Ling Liu Kai Li Jiaxi Chen Gang Wang Tianwen Gao Chunying Li Qiang Li
author_sort	Jun Tian
title	The Formation of Melanocyte Apoptotic Bodies in Vitiligo and the Relocation of Vitiligo Autoantigens under Oxidative Stress
title_short	The Formation of Melanocyte Apoptotic Bodies in Vitiligo and the Relocation of Vitiligo Autoantigens under Oxidative Stress
title_full	The Formation of Melanocyte Apoptotic Bodies in Vitiligo and the Relocation of Vitiligo Autoantigens under Oxidative Stress
title_fullStr	The Formation of Melanocyte Apoptotic Bodies in Vitiligo and the Relocation of Vitiligo Autoantigens under Oxidative Stress
title_full_unstemmed	The Formation of Melanocyte Apoptotic Bodies in Vitiligo and the Relocation of Vitiligo Autoantigens under Oxidative Stress
title_sort	formation of melanocyte apoptotic bodies in vitiligo and the relocation of vitiligo autoantigens under oxidative stress
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/cdf2cf55051a471b9e0ef7fed3a684e6
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The Formation of Melanocyte Apoptotic Bodies in Vitiligo and the Relocation of Vitiligo Autoantigens under Oxidative Stress

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