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Occludin Promotes Adhesion of CD8(+) T Cells and Melanocytes in Vitiligo via the HIF-1α Signaling Pathway

Loss of melanocytes induced by activated CD8(+) T cells is the pathological hallmark of vitiligo. Melanocyte-specific CD8(+) T cells are recruited to the skin via chemokines, thereby releasing perforin, granzyme, and other cytotoxic substances that destroy the melanocytes. However, the mechanism of...

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Autores principales: Zou, Puyu, Xiao, Yangfan, Deng, Qiancheng, Shi, Yaqian, You, Ruixuan, Pi, Zixin, Liu, Jiani, Zhan, Yi, Zeng, Qinghai, Zeng, Zhuotong, Xiao, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8865978/
https://www.ncbi.nlm.nih.gov/pubmed/35222802
http://dx.doi.org/10.1155/2022/6732972
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author Zou, Puyu
Xiao, Yangfan
Deng, Qiancheng
Shi, Yaqian
You, Ruixuan
Pi, Zixin
Liu, Jiani
Zhan, Yi
Zeng, Qinghai
Zeng, Zhuotong
Xiao, Rong
author_facet Zou, Puyu
Xiao, Yangfan
Deng, Qiancheng
Shi, Yaqian
You, Ruixuan
Pi, Zixin
Liu, Jiani
Zhan, Yi
Zeng, Qinghai
Zeng, Zhuotong
Xiao, Rong
author_sort Zou, Puyu
collection PubMed
description Loss of melanocytes induced by activated CD8(+) T cells is the pathological hallmark of vitiligo. Melanocyte-specific CD8(+) T cells are recruited to the skin via chemokines, thereby releasing perforin, granzyme, and other cytotoxic substances that destroy the melanocytes. However, the mechanism of CD8(+) T cells to adhere to melanocytes is unknown. Previous transcriptome sequencing results published by our group showed that the occluding (OCLN) gene was significantly upregulated in CD8(+) T cells from skin lesions of vitiligo. Occludin is a crucial component of the tight junction between cells; in cells without tight junction, occludin mediates the adhesion of two cells in the form of a self-ligand. This study demonstrated that OCLN gene expression was elevated in the CD8(+) T cells of vitiligo patients, and occludin mediates the adherence of CD8(+) T cells to melanocytes. Besides, pathological changes in vitiligo skin lesions reveal that CD8(+) T cells continuously persist in the skin lesions, which is related to the persistence of the disease. In this regard, we found that fibroblasts from vitiligo patients significantly express occludin, which may participate in the continuous retention of CD8(+) T cells in the skin lesions. The pathogenesis of vitiligo is closely related to oxidative stress, and our data suggest that overexpression of hypoxia-inducible factor-1α (HIF-1α) increases the expression of occludin. Besides, ChIP-qPCR of CD8(+) T cells revealed that HIF-1α directly binds to the OCLN promoter. Thus, occludin upregulation promotes the adhesion of CD8(+) T cells and melanocytes via the HIF-1α signaling pathway. Our study results suggested a critical role for OCLN in the occurrence, progression, and maintenance of vitiligo. Therefore, inhibiting the expression of OCLN gene may be a potential targeted treatment strategy.
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spelling pubmed-88659782022-02-24 Occludin Promotes Adhesion of CD8(+) T Cells and Melanocytes in Vitiligo via the HIF-1α Signaling Pathway Zou, Puyu Xiao, Yangfan Deng, Qiancheng Shi, Yaqian You, Ruixuan Pi, Zixin Liu, Jiani Zhan, Yi Zeng, Qinghai Zeng, Zhuotong Xiao, Rong Oxid Med Cell Longev Research Article Loss of melanocytes induced by activated CD8(+) T cells is the pathological hallmark of vitiligo. Melanocyte-specific CD8(+) T cells are recruited to the skin via chemokines, thereby releasing perforin, granzyme, and other cytotoxic substances that destroy the melanocytes. However, the mechanism of CD8(+) T cells to adhere to melanocytes is unknown. Previous transcriptome sequencing results published by our group showed that the occluding (OCLN) gene was significantly upregulated in CD8(+) T cells from skin lesions of vitiligo. Occludin is a crucial component of the tight junction between cells; in cells without tight junction, occludin mediates the adhesion of two cells in the form of a self-ligand. This study demonstrated that OCLN gene expression was elevated in the CD8(+) T cells of vitiligo patients, and occludin mediates the adherence of CD8(+) T cells to melanocytes. Besides, pathological changes in vitiligo skin lesions reveal that CD8(+) T cells continuously persist in the skin lesions, which is related to the persistence of the disease. In this regard, we found that fibroblasts from vitiligo patients significantly express occludin, which may participate in the continuous retention of CD8(+) T cells in the skin lesions. The pathogenesis of vitiligo is closely related to oxidative stress, and our data suggest that overexpression of hypoxia-inducible factor-1α (HIF-1α) increases the expression of occludin. Besides, ChIP-qPCR of CD8(+) T cells revealed that HIF-1α directly binds to the OCLN promoter. Thus, occludin upregulation promotes the adhesion of CD8(+) T cells and melanocytes via the HIF-1α signaling pathway. Our study results suggested a critical role for OCLN in the occurrence, progression, and maintenance of vitiligo. Therefore, inhibiting the expression of OCLN gene may be a potential targeted treatment strategy. Hindawi 2022-02-16 /pmc/articles/PMC8865978/ /pubmed/35222802 http://dx.doi.org/10.1155/2022/6732972 Text en Copyright © 2022 Puyu Zou et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zou, Puyu
Xiao, Yangfan
Deng, Qiancheng
Shi, Yaqian
You, Ruixuan
Pi, Zixin
Liu, Jiani
Zhan, Yi
Zeng, Qinghai
Zeng, Zhuotong
Xiao, Rong
Occludin Promotes Adhesion of CD8(+) T Cells and Melanocytes in Vitiligo via the HIF-1α Signaling Pathway
title Occludin Promotes Adhesion of CD8(+) T Cells and Melanocytes in Vitiligo via the HIF-1α Signaling Pathway
title_full Occludin Promotes Adhesion of CD8(+) T Cells and Melanocytes in Vitiligo via the HIF-1α Signaling Pathway
title_fullStr Occludin Promotes Adhesion of CD8(+) T Cells and Melanocytes in Vitiligo via the HIF-1α Signaling Pathway
title_full_unstemmed Occludin Promotes Adhesion of CD8(+) T Cells and Melanocytes in Vitiligo via the HIF-1α Signaling Pathway
title_short Occludin Promotes Adhesion of CD8(+) T Cells and Melanocytes in Vitiligo via the HIF-1α Signaling Pathway
title_sort occludin promotes adhesion of cd8(+) t cells and melanocytes in vitiligo via the hif-1α signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8865978/
https://www.ncbi.nlm.nih.gov/pubmed/35222802
http://dx.doi.org/10.1155/2022/6732972
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