系统性红斑狼疮中免疫失调特征的 PANoptosis 相关基因的分子特征。
Molecular characterization of PANoptosis-related genes with features of immune dysregulation in systemic lupus erythematosus.
机构信息
Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China; Department of Respiratory and Critical Care Medicine, Affiliated Jinling Hospital, Southeast University, Sch Med, Nanjing, China.
Department of Gastroenterology, Beijing Friendship Hospital, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease center, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Capital Medical University, Beijing, China.
出版信息
Clin Immunol. 2023 Aug;253:109660. doi: 10.1016/j.clim.2023.109660. Epub 2023 Jun 7.
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. PANoptosis is a novel form of programmed cell death involved in various inflammatory diseases. This study aimed to identify the differentially-expressed PANoptosis-related genes (PRGs) involved in immune dysregulation in SLE. Five key PRGs, including ZBP1, MEFV, LCN2, IFI27, and HSP90AB1, were identified. The prediction model with these 5 key PRGs showed a good diagnostic performance in distinguishing SLE patients from controls. These key PRGs were associated with memory B cells, neutrophils and CD8 + T cells. Besides, these key PRGs were significantly enriched in pathways involving the type I interferon responses and IL-6-JAK-STAT3 signaling. The expression levels of the key PRGs were validated in peripheral blood mononuclear cells (PBMCs) of patients with SLE. Our findings suggest that PANoptosis may be implicated in the immune dysregulation in SLE by regulating the interferons and JAK-STAT signaling pathways in memory B cells, neutrophils and CD8 + T cells.
系统性红斑狼疮（SLE）是一种异质性自身免疫性疾病。PANoptosis 是一种新的程序性细胞死亡形式，参与各种炎症性疾病。本研究旨在鉴定与 SLE 免疫失调相关的差异表达 PANoptosis 相关基因（PRGs）。鉴定到 5 个关键 PRGs，包括 ZBP1、MEFV、LCN2、IFI27 和 HSP90AB1。具有这 5 个关键 PRGs 的预测模型在区分 SLE 患者和对照方面表现出良好的诊断性能。这些关键 PRGs 与记忆 B 细胞、中性粒细胞和 CD8+T 细胞有关。此外，这些关键 PRGs 显著富集在涉及 I 型干扰素反应和 IL-6-JAK-STAT3 信号通路的途径中。关键 PRGs 的表达水平在 SLE 患者的外周血单核细胞（PBMCs）中得到验证。我们的研究结果表明，PANoptosis 可能通过调节记忆 B 细胞、中性粒细胞和 CD8+T 细胞中的干扰素和 JAK-STAT 信号通路，参与 SLE 的免疫失调。
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