title: Alarmin human α defensin HNP1 activates plasmacytoid dendritic cells by triggering NF-κB and IRF1 signaling pathways.
abstract: Human neutrophil peptide 1 (HNP1), a predominant α 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 IFNα upon treatment with HNP1. Additionally, HNP1 could promote CpG ODN-induced pDC production of proinflammatory cytokines including IFNα. HNP1 triggered activation of NF-κB and nuclear translocation of interferon regulatory factor 1 (IRF1) in CAL-1 cells. HNP1 upregulation of cytokine expression in pDCs was inhibited by blockade of NF-κB 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 IFNα production by human pDCs in vivo. Thus, HNP1 can activate human pDCs using NF-κB and IRF signaling pathways, and HNP-induced IFN production may participate in the inflammatory pathogenesis in certain authoimmune diseases such as rheumatoid arthritis.
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Research Center of Basic Medical Science, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Research Center of Basic Medical Science, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, People's Republic of China.
authors.forename: Linan
authors.initials: L
authors.lastname: Qiao
authors.affiliation: Department of Rheumatism and Immunology, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Lv
authors.affiliation: Basic Science Program, Leidos Biomedical Research Inc., and Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research (FNLCR), 1050 Boyles Street, Frederick, MD 21702, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Trivett
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Research Center of Basic Medical Science, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: Basic Science Program, Leidos Biomedical Research Inc., and Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research (FNLCR), 1050 Boyles Street, Frederick, MD 21702, USA.
authors.forename: Joost J
authors.initials: JJ
authors.lastname: Oppenheim
authors.affiliation: Basic Science Program, Leidos Biomedical Research Inc., and Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research (FNLCR), 1050 Boyles Street, Frederick, MD 21702, USA. Electronic address: yangd@mail.nih.gov.
authors.forename: De
authors.lastname: Yang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Research Center of Basic Medical Science, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, People's Republic of China. Electronic address: zhangning@tmu.edu.cn.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism*; D016898:Interferon-alpha / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D023084:alpha-Defensins / Q000378:metabolism*
chemical_list: C408982:CPG-oligonucleotide; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D016898:Interferon-alpha; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D023084:alpha-Defensins; C406413:human neutrophil peptide 1
keywords: Alarmin; Defensin; HNP1; IFN; pDC