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.