Table4_Single-cell profiling of peripheral blood and muscle cells reveals inflammatory features of juvenile dermatomyositis.XLS

Introduction: Juvenile dermatomyositis (JDM) is a rare yet serious childhood systemic autoimmune condition that primarily causes skin rashes and inflammatory myopathy of the proximal muscles. Although the associated immune response involves the innate and adaptive arms, a detailed analysis of the pertinent immune cells remains to be performed. This study aims to investigate the dynamic changes of cell type, cell composition and transcriptional profiles in peripheral blood and muscle tissues, and in order to clarify the involvement of immune cells in the pathogenesis of JDM and provide a theoretical reference for JDM.
Methods: Single-cell RNA sequencing combined with bioinformatic analyses were used to investigate the dynamic changes in cell composition and transcriptional profiles.
Results: Analysis of 45,859 cells revealed nine and seven distinct cell subsets in the peripheral blood and muscle tissues respectively. IFITM2+ and CYP4F3+ monocytes were largely produced, and CD74+ smooth muscle cells (SMCs) and CCL19+ fibroblasts were identified as inflammatory-related cell subtypes in JDM patients, exhibiting patient-specific cell population heterogeneity.The dynamic gene expression patterns presented an enhanced type I interferon response in peripheral blood monocytes and T-cells, and SMCs and fibroblasts in muscle of untreated JDM patients. EGR1 and IRF7 may play central roles in the inflammation in both CD74+ SMCs and CCL19+ fibroblasts. Moreover, inflammatory-related monocytes could regulate T-cells, and the interaction between immune cells and SMCs or fibroblasts in muscle was enhanced under the inflammatory state.
Conclusions: Immune dysregulation is one of the key pathogenic factors of JDM, and type I interferon responses are significantly enhanced in peripheral blood Monos and T cells as well as SMCs and fibroblasts. EGR1 and IRF7 may play central roles in the inflammation and are considered as potential therapeutic targets for JDM.

引言：青少年皮肌炎（Juvenile dermatomyositis, JDM）是一种罕见但严重的儿童全身性自身免疫性疾病，主要引发皮疹及近端肌肉炎症性肌病。尽管其相关免疫应答涉及先天免疫与适应性免疫分支，但针对相关免疫细胞的详细分析仍有待完成。本研究旨在探究外周血与肌肉组织中细胞类型、细胞组成及转录谱的动态变化，以明确免疫细胞在JDM发病机制中的作用，并为JDM提供理论参考。
方法：本研究采用单细胞RNA测序联合生物信息学分析的方法，探究细胞组成与转录谱的动态变化。
结果：对45859个细胞的分析显示，外周血与肌肉组织中分别存在9种和7种独特的细胞亚群。研究发现IFITM2+与CYP4F3+单核细胞显著扩增，并鉴定出CD74+平滑肌细胞（SMCs）及CCL19+成纤维细胞为JDM患者中与炎症相关的细胞亚型，展现出患者特异性的细胞群异质性。动态基因表达模式显示，未接受治疗的JDM患者外周血单核细胞与T细胞，以及肌肉中的平滑肌细胞和成纤维细胞均呈现增强的I型干扰素应答。EGR1与IRF7可能在CD74+平滑肌细胞及CCL19+成纤维细胞的炎症反应中发挥核心作用。此外，炎症相关单核细胞可调控T细胞，且炎症状态下肌肉中免疫细胞与平滑肌细胞或成纤维细胞间的相互作用得以增强。
结论：免疫失调是JDM的关键致病因素之一，外周血单核细胞、T细胞以及平滑肌细胞与成纤维细胞中的I型干扰素应答均显著增强。EGR1与IRF7可能在炎症反应中发挥核心作用，可被视为JDM潜在的治疗靶点。