Single-Cell transcriptional profiling reveals immune dysregulation and abnormal immune-inflammatory communications between immune and retinal cells in uveitis

Uveitis is an immune-inflammatory disease that can cause blindness. However, little is known about a comprehensive atlas of the ocular cellular and inflammatory components in uveitis. Here, single-cell RNA sequencing was performed to construct a transcriptomic atlas of ocular cells from experimental autoimmune uveitis (EAU) and control mice to identify disease- associated immune cell subsets and molecules. We reveal 15 cell types in eyes and found an α-Synuclein positive microglia subset and plasma cell subset with high level of cytokines. The heterogeneous plasma cells subsets communicated with DC, T cells and retinal cells via various cytokines and molecular pairing. The G protein Rab1A participated in the inflammatory response of plasma cells. Altogether, we revealed the heterogeneous inflammatory genes, EAU-specific immune cell populations, and dysregulated communications of immune and retinal cells in EAU. This result provides a systematic view of the transcriptional map of uveitis and a foundation for studying the cellular and molecular mechanisms and pathogenesis of this disease. Eye tissues from 15 EAU mice (after immunization for 16 days) vs eye tissues from 15 Control mice. Eye tissues of each 15 mice were combined into one sample.

葡萄膜炎（Uveitis）是一种可导致失明的免疫炎症性疾病。然而，目前学界对葡萄膜炎眼部细胞及炎症组分的全面图谱仍知之甚少。本研究通过单细胞RNA测序（single-cell RNA sequencing），构建了实验性自身免疫性葡萄膜炎（experimental autoimmune uveitis, EAU）小鼠与对照小鼠眼部细胞的转录组图谱，旨在鉴定疾病相关免疫细胞亚群及分子。我们在眼部组织中共鉴定出15种细胞类型，并发现了α-突触核蛋白（α-Synuclein）阳性小胶质细胞亚群，以及高表达细胞因子的浆细胞亚群。异质性浆细胞亚群可通过多种细胞因子与分子配对机制，与树突状细胞（DC）、T细胞及视网膜细胞发生通信互作。G蛋白Rab1A参与了浆细胞的炎症应答过程。综上，本研究揭示了EAU模型中存在的异质性炎症基因、EAU特异性免疫细胞群，以及免疫细胞与视网膜细胞间的失调通信网络。本研究为葡萄膜炎的转录组图谱提供了系统性研究视角，同时为阐明该疾病的细胞与分子机制及发病机制奠定了基础。本研究的样本包括15只EAU小鼠（免疫造模16天后）的眼部组织与15只对照小鼠的眼部组织；每15只小鼠的眼部组织合并为一个样本。