Phospholipid Scramblase 1 regulates Toll-like receptor 9-mediated type Ⅰ interferon prod

Phospholipid Scramblase 1 regulates Toll-like receptor 9-mediated type Ⅰ interferon production

in plasmacytoid dendritic cells

Amjad

H

Talukder;Musheng

Bao;Tae

Whan

Kim;Valeria

Facchinetti;Shino

Hanabuchi;Laura Bover;Tomasz Zal;Yong-Jun Liu

【期刊名称】《细胞研究（英文版）》 【年(卷),期】2012(022)007

【摘要】Toll-like receptor 9 (TLR9) senses microbial DNA in the endosomes of plasmacytoid dendritic cells (pDCs) and triggers MyD88-dependent type 1 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 PLSCRl-deficient mice.Our study demonstrates that PLSCR1 is a TLR9-interacting protein that plays an important role in pDC's type 1