Expression of Interferon Regulatory Factor 8 (IRF8) and Its Association with Infections in Dialysis Patients

• Published in: Cells (Basel, Switzerland) Switzerland), 2023-07, Vol.12 (14), p.1892
• Main Authors: Friebus-Kardash, Justa, Kuang, Fei, Peitz, Tobias, Hamdan, Thamer A, Eisenberger, Ute, Boss, Kristina, Kribben, Andreas, Lang, Karl Sebastian, Jahn, Michael
• Format: Article
• Language: English
• Subjects: Blood & organ donations; Complications and side effects; Dendritic cells; Dialysis; Flow cytometry; Gene expression; Genetic aspects; Health aspects; Hemodialysis; Hospitalization; Immune system; Infections; Interferon; Interferon regulatory factor; interferon regulatory factor 8 (IRF8); Leukocytes; Macrophages; Monocytes; Mortality; Natural killer cells; Peritoneal dialysis; Plasmacytoid cells; Pneumonia; Risk factors; Sepsis; Software; Transcription factors
• ISSN: 2073-4409; 2073-4409
• 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.