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Identification of Hif1α as a Potential Participant in Autoimmune Uveitis Pathogenesis Using Single-Cell Transcriptome Analysis

PURPOSE: This study purposed to depict the transcriptional changes associated with autoimmune uveitis (AU) pathogenesis and identify potential therapeutic targets of this disease. METHODS: An experimental AU (EAU) model was established with retina antigen and adjuvants. An EAU control group was esta...

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Autores principales: Zhu, Lei, Li, He, Wang, Rong, Li, Zhaohuai, Zhao, Sichen, Peng, Xuening, Su, Wenru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10214869/
https://www.ncbi.nlm.nih.gov/pubmed/37227746
http://dx.doi.org/10.1167/iovs.64.5.24
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author Zhu, Lei
Li, He
Wang, Rong
Li, Zhaohuai
Zhao, Sichen
Peng, Xuening
Su, Wenru
author_facet Zhu, Lei
Li, He
Wang, Rong
Li, Zhaohuai
Zhao, Sichen
Peng, Xuening
Su, Wenru
author_sort Zhu, Lei
collection PubMed
description PURPOSE: This study purposed to depict the transcriptional changes associated with autoimmune uveitis (AU) pathogenesis and identify potential therapeutic targets of this disease. METHODS: An experimental AU (EAU) model was established with retina antigen and adjuvants. An EAU control group was established with adjuvant only to eliminate nonspecific effects. We conducted single-cell RNA sequencing (scRNA-seq) on cervical draining lymph node cells of EAU, EAU control, and normal mice to identify the EAU-associated transcriptional changes and the potential pathogenic molecules. Subsequent flow cytometry, adoptive transfer experiment, scRNA-seq analysis of human uveitis, and proliferation assessment were conducted to verify the function of the interested molecule in uveitis. RESULTS: The scRNA-seq data suggested that hypoxia-inducible factor 1 alpha (Hif1α) may participate in EAU pathogenesis via regulating T helper (Th)-17, Th1, and regulatory T cells. Hif1α inhibition alleviated EAU symptoms and regulated Th17, Th1, and regulatory T cell proportions. CD4(+) T cells with repressed Hif1α expression failed to transfer EAU to naïve mice. In Vogt–Koyanagi–Harada disease, which is a human uveitis, Hif1α was also increased in CD4(+) T cells and regulated their proliferation. CONCLUSIONS: The results indicate that Hif1α may participate in AU pathogenesis and are, thus, a potential therapeutic target.
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spelling pubmed-102148692023-05-27 Identification of Hif1α as a Potential Participant in Autoimmune Uveitis Pathogenesis Using Single-Cell Transcriptome Analysis Zhu, Lei Li, He Wang, Rong Li, Zhaohuai Zhao, Sichen Peng, Xuening Su, Wenru Invest Ophthalmol Vis Sci Immunology and Microbiology PURPOSE: This study purposed to depict the transcriptional changes associated with autoimmune uveitis (AU) pathogenesis and identify potential therapeutic targets of this disease. METHODS: An experimental AU (EAU) model was established with retina antigen and adjuvants. An EAU control group was established with adjuvant only to eliminate nonspecific effects. We conducted single-cell RNA sequencing (scRNA-seq) on cervical draining lymph node cells of EAU, EAU control, and normal mice to identify the EAU-associated transcriptional changes and the potential pathogenic molecules. Subsequent flow cytometry, adoptive transfer experiment, scRNA-seq analysis of human uveitis, and proliferation assessment were conducted to verify the function of the interested molecule in uveitis. RESULTS: The scRNA-seq data suggested that hypoxia-inducible factor 1 alpha (Hif1α) may participate in EAU pathogenesis via regulating T helper (Th)-17, Th1, and regulatory T cells. Hif1α inhibition alleviated EAU symptoms and regulated Th17, Th1, and regulatory T cell proportions. CD4(+) T cells with repressed Hif1α expression failed to transfer EAU to naïve mice. In Vogt–Koyanagi–Harada disease, which is a human uveitis, Hif1α was also increased in CD4(+) T cells and regulated their proliferation. CONCLUSIONS: The results indicate that Hif1α may participate in AU pathogenesis and are, thus, a potential therapeutic target. The Association for Research in Vision and Ophthalmology 2023-05-25 /pmc/articles/PMC10214869/ /pubmed/37227746 http://dx.doi.org/10.1167/iovs.64.5.24 Text en Copyright 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Immunology and Microbiology
Zhu, Lei
Li, He
Wang, Rong
Li, Zhaohuai
Zhao, Sichen
Peng, Xuening
Su, Wenru
Identification of Hif1α as a Potential Participant in Autoimmune Uveitis Pathogenesis Using Single-Cell Transcriptome Analysis
title Identification of Hif1α as a Potential Participant in Autoimmune Uveitis Pathogenesis Using Single-Cell Transcriptome Analysis
title_full Identification of Hif1α as a Potential Participant in Autoimmune Uveitis Pathogenesis Using Single-Cell Transcriptome Analysis
title_fullStr Identification of Hif1α as a Potential Participant in Autoimmune Uveitis Pathogenesis Using Single-Cell Transcriptome Analysis
title_full_unstemmed Identification of Hif1α as a Potential Participant in Autoimmune Uveitis Pathogenesis Using Single-Cell Transcriptome Analysis
title_short Identification of Hif1α as a Potential Participant in Autoimmune Uveitis Pathogenesis Using Single-Cell Transcriptome Analysis
title_sort identification of hif1α as a potential participant in autoimmune uveitis pathogenesis using single-cell transcriptome analysis
topic Immunology and Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10214869/
https://www.ncbi.nlm.nih.gov/pubmed/37227746
http://dx.doi.org/10.1167/iovs.64.5.24
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