State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, 510060, Guangzhou, China.
Research Unit of Ocular Development and Regeneration, Chinese Academy of Medical Sciences, 100085, Beijing, China.
Commun Biol. 2023 Oct 17;6(1):1048. doi: 10.1038/s42003-023-05420-x.
Behect's disease is a chronic vasculitis characterized by complex multi-organ immune aberrations. However, a comprehensive understanding of the gene-regulatory profile of peripheral autoimmunity and the diverse immune responses across distinct cell types in Behcet's disease (BD) is still lacking. Here, we present a multi-omic single-cell study of 424,817 cells in BD patients and non-BD individuals. This study maps chromatin accessibility and gene expression in the same biological samples, unraveling vast cellular heterogeneity. We identify widespread cell-type-specific, disease-associated active and pro-inflammatory immunity in both transcript and epigenomic aspects. Notably, integrative multi-omic analysis reveals putative TF regulators that might contribute to chromatin accessibility and gene expression in BD. Moreover, we predicted gene-regulatory networks within nominated TF activators, including AP-1, NF-kB, and ETS transcript factor families, which may regulate cellular interaction and govern inflammation. Our study illustrates the epigenetic and transcriptional landscape in BD peripheral blood and expands understanding of potential epigenomic immunopathology in this disease.
贝赫切特病是一种慢性血管炎，其特征是复杂的多器官免疫异常。然而，对于贝赫切特病（BD）外周自身免疫的基因调控特征以及不同细胞类型中的多种免疫反应，我们仍缺乏全面的了解。在这里，我们对 424817 个 BD 患者和非 BD 个体的细胞进行了多组学单细胞研究。这项研究在同一生物样本中绘制了染色质可及性和基因表达图谱，揭示了广泛的细胞类型特异性、疾病相关的活跃和促炎免疫。值得注意的是，整合的多组学分析揭示了可能有助于 BD 中染色质可及性和基因表达的潜在 TF 调节因子。此外，我们预测了提名 TF 激活剂内的基因调控网络，包括 AP-1、NF-kB 和 ETS 转录因子家族，这些可能调节细胞间相互作用并控制炎症。我们的研究说明了 BD 外周血中的表观遗传学和转录组学景观，并扩展了对这种疾病潜在的表观遗传免疫病理学的理解。
