Comprehensive analysis of a mouse model of spontaneous uveoretinitis using single-cell RNA sequencing.
basic_science · Level V
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- Record sourced from PubMed, PMID 31843893.
- Also identified by DOI 10.1073/pnas.1915571116 and PMC identifier 6936593.
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Abstract
Autoimmune uveoretinitis is a significant cause of visual loss, and mouse models offer unique opportunities to study its disease mechanisms. <i>Aire</i><sup><i>-/-</i></sup> 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 <i>Aire</i><sup><i>-/-</i></sup> 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 <i>Aire</i><sup>-/-</sup> 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 <i>Aire</i><sup>-/-</sup> 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.