Division of Pediatric Rheumatology/Immunology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States.
Department of Biomedical Engineering, Washington University, St. Louis, MO, United States.
Front Immunol. 2022 Oct 31;13:1007022. doi: 10.3389/fimmu.2022.1007022. eCollection 2022.
Juvenile dermatomyositis (JDM) is a pediatric autoimmune disease associated with characteristic rash and proximal muscle weakness. To gain insight into differential lymphocyte gene expression in JDM, peripheral blood mononuclear cells from 4 new-onset JDM patients and 4 healthy controls were sorted into highly enriched lymphocyte populations for RNAseq analysis. NK cells from JDM patients had substantially greater differentially expressed genes (273) than T (57) and B (33) cells. Upregulated genes were associated with the innate immune response and cell cycle, while downregulated genes were associated with decreased ribosomal RNA. Suppressed ribosomal RNA in JDM NK cells was validated by measuring transcription and phosphorylation levels. We confirmed a population of low ribosome expressing NK cells in healthy adults and children. This population of low ribosome NK cells was substantially expanded in 6 treatment-naïve JDM patients and was associated with decreased NK cell degranulation. The enrichment of this NK low ribosome population was completely abrogated in JDM patients with quiescent disease. Together, these data suggest NK cells are highly activated in new-onset JDM patients with an increased population of low ribosome expressing NK cells, which correlates with decreased NK cell function and resolved with control of active disease.
幼年特发性皮肌炎（JDM）是一种与特征性皮疹和近端肌肉无力相关的儿科自身免疫性疾病。为了深入了解 JDM 中差异淋巴细胞基因表达，我们从 4 例新发 JDM 患者和 4 例健康对照者的外周血单核细胞中分离出高度富集的淋巴细胞群体，进行 RNAseq 分析。与 T（57）和 B（33）细胞相比，JDM 患者的 NK 细胞具有更多的差异表达基因（273 个）。上调的基因与先天免疫反应和细胞周期有关，而下调的基因与核糖体 RNA 减少有关。通过测量转录和磷酸化水平，我们验证了 JDM NK 细胞中核糖体 RNA 的抑制。我们在健康成年人和儿童中证实了存在低核糖体表达 NK 细胞的群体。在 6 例未经治疗的 JDM 患者中，这种低核糖体 NK 细胞群体显著扩增，并与 NK 细胞脱颗粒减少相关。在疾病静止的 JDM 患者中，这种 NK 低核糖体群体的富集完全被消除。总之，这些数据表明，新发 JDM 患者的 NK 细胞高度激活，并且存在低核糖体表达 NK 细胞的群体增加，这与 NK 细胞功能下降有关，而随着疾病活动的控制，NK 细胞功能下降得到缓解。
