title: PACSIN1 regulates the TLR7/9-mediated type I interferon response in plasmacytoid dendritic cells.
abstract: Plasmacytoid dendritic cells (pDCs) are the professional interferon (IFN)-producing cells of the immune system. pDCs specifically express Toll-like receptor (TLR)7 and TLR9 molecules and produce massive amounts of type I IFN by sensing microbial nucleic acids via TLR7 and TLR9. Here we report that protein kinase C and casein kinase substrate in neurons (PACSIN) 1, is specifically expressed in human and mouse pDCs. Knockdown of PACSIN1 by short hairpin RNA (shRNA) in a human pDC cell line significantly inhibited the type I IFN response of the pDCs to TLR9 ligand. PACSIN1-deficient mice exhibited normal levels of conventional DCs and pDCs, demonstrating that development of pDCs was intact although PACSIN1-deficient pDCs showed reduced levels of IFN-α production in response to both cytosine guanine dinucleotide (CpG)-oligonucleotide (ODN) and virus. In contrast, the production of proinflammatory cytokines in response to those ligands was not affected in PACSIN1-deficient pDCs, suggesting that PACSIN1 represents a pDC-specific adaptor molecule that plays a specific role in the type I IFN signaling cascade.
authors.affiliation: Department of Immunology and Center for Cancer Immunology Research, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Eiji
authors.initials: E
authors.lastname: Esashi
authors.forename: Musheng
authors.initials: M
authors.lastname: Bao
authors.forename: Yi-Hong
authors.initials: YH
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D015151:Immunoblotting; D007150:Immunohistochemistry; D007370:Interferon Type I / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D051199:Toll-Like Receptor 7 / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007370:Interferon Type I; C492182:PACSIN1 protein, human; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D012313:RNA