Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, 47057 Essen, Germany.
Institute of Immunology, University Hospital Essen, University of Duisburg-Essen, 47057 Essen, Germany.
Cells. 2023 Jul 19;12(14):1892. doi: 10.3390/cells12141892.
Patients on dialysis have dysfunctions of innate and adaptive immune system responses. The transcriptional factor IRF8 (interferon regulatory factor 8) is primarily expressed in plasmacytoid cells (pDCs) and myeloid dendritic cells (mDCs), playing a crucial role in the maturation of dendritic cells, monocytes, and macrophages, and contributing to protection against bacterial infections. The current study analyzed the expression patterns of IRF8 and assessed its association with the risk of infections in 79 dialysis patients compared to 44 healthy controls. Different subsets of leukocytes and the intracellular expression of IRF8 were measured using flow cytometry. Compared to the healthy controls, the dialysis patients showed significantly reduced numbers of pDCs and significantly increased numbers of natural killer cells and classical and intermediate monocytes. The dialysis patients exhibited decreased numbers of IRF8-positive dendritic cells (pDC < 0.001, mDC1 < 0.001, mDC2 = 0.005) and increased numbers of IRF8-positive monocytes ( < 0.001). IRF8 expression in pDC, mDC, and classical monocytes was lower in the dialysis patients than in the controls. Dialysis patients who required hospitalization due to infections within one year of follow-up displayed significantly reduced IRF8 expression levels in pDCs compared to patients without such infections ( = 0.04). Our results suggest that reduced IRF8 expression in pDCs is a potential risk factor predisposing dialysis patients to serious infections.
透析患者的先天和适应性免疫系统功能失调。转录因子 IRF8（干扰素调节因子 8）主要在浆细胞样树突状细胞（pDC）和髓样树突状细胞（mDC）中表达，在树突状细胞、单核细胞和巨噬细胞的成熟中发挥关键作用，并有助于预防细菌感染。本研究分析了 79 名透析患者和 44 名健康对照者中 IRF8 的表达模式，并评估其与感染风险的相关性。采用流式细胞术检测白细胞的不同亚群和 IRF8 的细胞内表达。与健康对照组相比，透析患者的 pDC 数量明显减少，NK 细胞和经典单核细胞和中间单核细胞数量明显增加。透析患者的 IRF8 阳性树突状细胞（pDC < 0.001，mDC1 < 0.001，mDC2 = 0.005）数量减少，IRF8 阳性单核细胞（ < 0.001）数量增加。与对照组相比，透析患者 pDC、mDC 和经典单核细胞中的 IRF8 表达水平较低。在随访 1 年内因感染而需要住院治疗的透析患者的 pDC 中，IRF8 表达水平明显低于未发生感染的患者（ = 0.04）。我们的研究结果表明，pDC 中 IRF8 表达降低是透析患者发生严重感染的潜在危险因素。
