Marshall Lysette, Raychaudhuri Soumya, Viatte Sebastien
Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK.
Center for Data Sciences, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Nat Rev Rheumatol. 2025 May 7. doi: 10.1038/s41584-025-01253-6.
Autoimmune rheumatic diseases are a heterogeneous group of conditions, including rheumatoid arthritis (RA) and systemic lupus erythematosus. With the increasing availability of large single-cell datasets, novel disease-associated cell types continue to be identified and characterized at multiple omics layers, for example, 'T peripheral helper' (T) (CXCR5 PD-1) cells in RA and systemic lupus erythematosus and MerTK myeloid cells in RA. Despite efforts to define disease-relevant cell atlases, the very definition of a 'cell type' or 'lineage' has proven controversial as higher resolution assays emerge. This Review explores the cell types and states involved in disease pathogenesis, with a focus on the shifting perspectives on immune and stromal cell taxonomy. These understandings of cell identity are closely related to the computational methods adopted for analysis, with implications for the interpretation of single-cell data. Understanding the underlying cellular architecture of disease is also crucial for therapeutic research as ambiguity hinders translation to the clinical setting. We discuss the implications of different frameworks for cell identity for disease treatment and the discovery of predictive biomarkers for stratified medicine - an unmet clinical need for autoimmune rheumatic diseases.
自身免疫性风湿性疾病是一组异质性疾病，包括类风湿关节炎（RA）和系统性红斑狼疮。随着大型单细胞数据集越来越容易获得，新的疾病相关细胞类型不断在多个组学层面被识别和表征，例如，RA和系统性红斑狼疮中的“外周辅助性T”（Th）（CXCR5 PD-1）细胞以及RA中的MerTK髓样细胞。尽管人们努力定义与疾病相关的细胞图谱，但随着分辨率更高的检测方法出现，“细胞类型”或“谱系”的定义已被证明存在争议。本综述探讨了疾病发病机制中涉及的细胞类型和状态，重点关注免疫和基质细胞分类学的不断变化的观点。这些对细胞身份的理解与用于分析的计算方法密切相关，对单细胞数据的解释具有重要意义。了解疾病的潜在细胞结构对于治疗研究也至关重要，因为模糊性阻碍了向临床应用的转化。我们讨论了不同细胞身份框架对疾病治疗的影响以及分层医学预测性生物标志物的发现——这是自身免疫性风湿性疾病尚未满足的临床需求。
