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Publication : PACSIN1 regulates the TLR7/9-mediated type I interferon response in plasmacytoid dendritic cells.

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.
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