Zeng Liuting, Yang Kailin, Zhang Tianqing, Zhu Xiaofei, Hao Wensa, Chen Hua, Ge Jinwen
Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Beijing, China.
Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China.
J Autoimmun. 2022 Dec;133:102919. doi: 10.1016/j.jaut.2022.102919. Epub 2022 Oct 12.
Autoimmunity refers to the phenomenon that the body's immune system produces antibodies or sensitized lymphocytes to its own tissues to cause an immune response. Immune disorders caused by autoimmunity can mediate autoimmune diseases. Autoimmune diseases have complicated pathogenesis due to the many types of cells involved, and the mechanism is still unclear. The emergence of single-cell research technology can solve the problem that ordinary transcriptome technology cannot be accurate to cell type. It provides unbiased results through independent analysis of cells in tissues and provides more mRNA information for identifying cell subpopulations, which provides a novel approach to study disruption of immune tolerance and disturbance of pro-inflammatory pathways on a cellular basis. It may fundamentally change the understanding of molecular pathways in the pathogenesis of autoimmune diseases and develop targeted drugs. Single-cell transcriptome sequencing (scRNA-seq) has been widely applied in autoimmune diseases, which provides a powerful tool for demonstrating the cellular heterogeneity of tissues involved in various immune inflammations, identifying pathogenic cell populations, and revealing the mechanism of disease occurrence and development. This review describes the principles of scRNA-seq, introduces common sequencing platforms and practical procedures, and focuses on the progress of scRNA-seq in 41 autoimmune diseases, which include 9 systemic autoimmune diseases and autoinflammatory diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.) and 32 organ-specific autoimmune diseases (5 Skin diseases, 3 Nervous system diseases, 4 Eye diseases, 2 Respiratory system diseases, 2 Circulatory system diseases, 6 Liver, Gallbladder and Pancreas diseases, 2 Gastrointestinal system diseases, 3 Muscle, Bones and joint diseases, 3 Urinary system diseases, 2 Reproductive system diseases). This review also prospects the molecular mechanism targets of autoimmune diseases from the multi-molecular level and multi-dimensional analysis combined with single-cell multi-omics sequencing technology (such as scRNA-seq, Single cell ATAC-seq and single cell immune group library sequencing), which provides a reference for further exploring the pathogenesis and marker screening of autoimmune diseases and autoimmune inflammatory diseases in the future.
自身免疫是指机体免疫系统针对自身组织产生抗体或致敏淋巴细胞，从而引发免疫反应的现象。由自身免疫引起的免疫紊乱可介导自身免疫性疾病。由于涉及的细胞类型众多，自身免疫性疾病的发病机制复杂，目前其机制仍不明确。单细胞研究技术的出现能够解决普通转录组技术无法精确到细胞类型的问题。它通过对组织中的细胞进行独立分析，提供无偏倚的结果，并为识别细胞亚群提供更多的mRNA信息，这为在细胞水平上研究免疫耐受破坏和促炎途径紊乱提供了一种新方法。它可能从根本上改变对自身免疫性疾病发病机制中分子途径的认识，并开发出靶向药物。单细胞转录组测序（scRNA-seq）已广泛应用于自身免疫性疾病研究，为证明各种免疫炎症所涉及组织的细胞异质性、识别致病细胞群体以及揭示疾病发生发展机制提供了强大工具。本综述阐述了scRNA-seq的原理，介绍了常见的测序平台和实际操作流程，并重点关注scRNA-seq在41种自身免疫性疾病中的研究进展，其中包括9种系统性自身免疫性疾病和自身炎症性疾病（类风湿关节炎、系统性红斑狼疮等）以及32种器官特异性自身免疫性疾病（5种皮肤病、3种神经系统疾病、4种眼科疾病、2种呼吸系统疾病、2种循环系统疾病、6种肝胆胰疾病、2种胃肠道系统疾病、3种肌肉骨骼和关节疾病、3种泌尿系统疾病、2种生殖系统疾病）。本综述还结合单细胞多组学测序技术（如scRNA-seq、单细胞ATAC-seq和单细胞免疫组库测序），从多分子水平和多维度分析对自身免疫性疾病的分子机制靶点进行了展望，为未来进一步探索自身免疫性疾病和自身免疫性炎症性疾病的发病机制及标志物筛选提供参考。
