First Author | Esashi E | Year | 2012 |
Journal | Eur J Immunol | Volume | 42 |
Issue | 3 | Pages | 573-9 |
PubMed ID | 22488361 | Mgi Jnum | J:187784 |
Mgi Id | MGI:5438186 | Doi | 10.1002/eji.201142045 |
Citation | Esashi E, et al. (2012) PACSIN1 regulates the TLR7/9-mediated type I interferon response in plasmacytoid dendritic cells. Eur J Immunol 42(3):573-9 |
abstractText | 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-alpha 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. |