Alarmin human a defensin HNP1 activates plasmacytoid dendritic cells by triggering NF-κB and IRF1 signaling pathways

作者：Wang, Fang; Qiao, Linan; Lv, Xing; Trivett, Anna; Yang, Rui; Oppenheim, Joost J.; Yang, De^*; Zhang, Ning^*

来源：Cytokine, 2016, 83: 53-60.

DOI：10.1016/j.cyto.2016.03.015

• Defensin
• HNP1
• pDC
• Alarmin
• IFN

Human neutrophil peptide 1 (HNP1), a predominant alpha defensin in the azurophilic granules of human neutrophils, is an alarmin capable of inducing the migration and maturation of human myeloid/conventional dendritic cells. However, it is not determined whether it can activate plasmacytoid dendritic cells (pDCs). Herein, we found that both human pDCs and CAL-1 cells, a pDC-like cell line, produced IFN alpha upon treatment with HNP1. Additionally, HNP1 could promote CpG ODN-induced pDC production of proinflammatory cytokines including IFN alpha. HNP1 triggered activation of NF-kappa B and nuclear translocation of interferon regulatory factor 1 (IRFI) in CAL-1 cells. HNP1 upregulation of cytokine expression in pDCs was inhibited by blockade of NF-kappa B activation or knockdown of IRF1, demonstrating the importance of these two signaling events in HNP1-induced pDC activation. Using a human pDC-nude mouse model, HNP1 was shown to induce IFN alpha, production by human pDCs in vivo. Thus, HNP1 can activate human pDCs using NF-kappa B and IRF signaling pathways, and HNP-induced IFN production may participate in the inflammatory pathogenesis in certain authoimmune diseases such as rheumatoid arthritis.

• 出版日期2016-7
• 单位天津医科大学