Plasmacytoid dendritic cells (PDCs) are critical for defense against respiratory viruses because of their propensity to secrete high levels of type I interferons (IFN). The functions of PDCs in the lung can be influenced by airway epithelial cells. We examined the effect of human primary bronchial epithelial cells (PBECs) on PDC functions by performing RNA-sequencing of PDCs after co-culture with air liquid interface differentiated PBECs. Functional analysis revealed that PDCs co-cultured with PBECs displayed upregulation of type I IFN production and response genes. Upregulated transcripts included those encoding cytosolic sensors of DNA, ZBP-1,IRF-3, and NFkB as well as genes involved in amplification of the IFN response, such as IFNAR1, JAK/STAT, ISG15. In keeping with the RNA-seq data, we observe increased secretion of type I IFN and other cytokines in response to influenza in PDCs co-cultured with PBECs. The PDCs also primed Th1 responses in T cells. The enhanced response of PDCs co-cultured with PBECs was due to the action of growth factors, GMCSF, GCSF, and VEGF, which were secreted by PBECs on differentiation. These data highlight possible mechanisms to enhance the production of type-I IFN in the airways, which is critical for host defense against respiratory infections.

中文翻译：

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气道上皮细胞启动浆细胞样树突状细胞，通过分泌生长因子对病原体作出反应。

浆细胞样树突状细胞 (PDC) 对于防御呼吸道病毒至关重要，因为它们倾向于分泌高水平的 I 型干扰素 (IFN)。肺中 PDC 的功能会受到气道上皮细胞的影响。我们通过在与气液界面分化的 PBEC 共培养后对 PDC 进行 RNA 测序，检查了人原代支气管上皮细胞 (PBEC) 对 PDC 功能的影响。功能分析表明，与 PBEC 共培养的 PDC 表现出 I 型干扰素产生和反应基因的上调。上调的转录物包括那些编码 DNA、ZBP-1、IRF-3 和 NFkB 的细胞溶质感受器的转录物，以及参与 IFN 反应放大的基因，例如 IFNAR1、JAK/STAT、ISG15。与 RNA-seq 数据一致，我们观察到在与 PBEC 共培养的 PDC 中，I 型干扰素和其他细胞因子的分泌增加以应对流感。PDC 还引发了 T 细胞中的 Th1 反应。PDCs 与 PBECs 共培养的增强反应是由于 PBECs 在分化过程中分泌的生长因子 GMCSF、GCSF 和 VEGF 的作用。这些数据突出了增强气道中 I 型干扰素产生的可能机制，这对于宿主防御呼吸道感染至关重要。