文章基本信息

标题：Comprehensive analysis of a mouse model of spontaneous uveoretinitis using single-cell RNA sequencing
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作者：Jacob S. Heng ; Sean F. Hackett ; Genevieve L. Stein-O’Brien 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2019
卷号：116
期号：52
页码：26734-26744
DOI：10.1073/pnas.1915571116
出版社：The National Academy of Sciences of the United States of America
摘要：Autoimmune uveoretinitis is a significant cause of visual loss, and mouse models offer unique opportunities to study its disease mechanisms. Aire −/− mice fail to express self-antigens in the thymus, exhibit reduced central tolerance, and develop a spontaneous, chronic, and progressive uveoretinitis. Using single-cell RNA sequencing (scRNA-seq), we characterized wild-type and Aire −/− retinas to define, in a comprehensive and unbiased manner, the cell populations and gene expression patterns associated with disease. Based on scRNA-seq, immunostaining, and in situ hybridization, we infer that 1) the dominant effector response in Aire −/− retinas is Th1-driven, 2) a subset of monocytes convert to either a macrophage/microglia state or a dendritic cell state, 3) the development of tertiary lymphoid structures constitutes part of the Aire −/− retinal phenotype, 4) all major resident retinal cell types respond to interferon gamma (IFNG) by changing their patterns of gene expression, and 5) Muller glia up-regulate specific genes in response to IFN gamma and may act as antigen-presenting cells.
关键词：Aire knockout ; mouse model ; ocular immunology ; single-cell RNAseq ; autoimmune uveitis