Interferon regulatory factor 7‐mediated responses are defective in cord blood plasmacytoid dendritic cells

Plasmacytoid dendritic cells (pDC) are specialized in massive production of type I interferons (IFN) upon viral infections. Activation of IFN regulatory factor (IRF)‐7 is critically required for the synthesis of type I IFN in pDC. IRF‐7 is highly expressed by resting pDC and translocates into the nucleus to initiate type I IFN transcription. In a previous work, we observed an impaired IFN‐α production in enriched cord blood pDC following a TLR9 stimulation using CpG oligonucleotides. Herein, we show that highly purified pDC from cord blood exhibit a profound defect in their capacity to produce IFN‐α/β in response to TLR9 as well as to TLR7 ligation or human CMV or HSV‐1 exposure. Microarray experiments indicate that expression of the majority of type I IFN subtypes induced by a TLR7 agonist is reduced in cord blood pDC. We next demonstrated a reduced nuclear translocation of IRF‐7 in cord blood pDC following CpG and HSV stimulation as compared to adult pDC. We conclude that impaired IRF‐7 translocation in cord blood pDC is associated with defective expression of type I IFN genes. Our data provide a molecular understanding for the decreased ability of cord blood pDC to produce type I IFN upon viral stimulation.

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