Phospholipid Scramblase 1 regulates Toll-like receptor 9-mediated type i interferon production in plasmacytoid dendritic cells Academic Article uri icon

Overview

MeSH Major

  • Dendritic Cells
  • Interferon Type I
  • Phospholipid Transfer Proteins
  • Toll-Like Receptor 9

abstract

  • Toll-like receptor 9 (TLR9) senses microbial DNA in the endosomes of plasmacytoid dendritic cells (pDCs) and triggers MyD88-dependent type I interferon (IFN) responses. To better understand TLR9 biology in pDCs, we established a yeast two-hybrid library for the identification of TLR9-interacting proteins. Here, we report that an IFN-inducible protein, phospholipid scramblase 1 (PLSCR1), interacts with TLR9 in pDCs. Knockdown of PLSCR1 expression by siRNA in human pDC cell line led to a 60-70% reduction of IFN-α responses following CpG-ODN (oligodeoxynucleotide) stimulation. Primary pDCs from PLSCR1-deficient mice produced lower amount of type 1 IFN than pDCs from the wild-type mice in response to CpG-ODN, herpes simplex virus and influenza A virus. Following CpG-A stimulation, there were much lower amounts of TLR9 in the early endosomes together with CpG-A in pDCs from PLSCR1-deficient mice. Our study demonstrates that PLSCR1 is a TLR9-interacting protein that plays an important role in pDC's type 1 IFN responses by regulating TLR9 trafficking to the endosomal compartment.

publication date

  • July 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3391020

Digital Object Identifier (DOI)

  • 10.1038/cr.2012.45

PubMed ID

  • 22453241

Additional Document Info

start page

  • 1129

end page

  • 39

volume

  • 22

number

  • 7