| Autor: |
Talukder AH; Department of Immunology, Center for Cancer Immunology Research, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Bao M, Kim TW, Facchinetti V, Hanabuchi S, Bover L, Zal T, Liu YJ |
| Jazyk: |
angličtina |
| Zdroj: |
Cell research [Cell Res] 2012 Jul; Vol. 22 (7), pp. 1129-39. Date of Electronic Publication: 2012 Mar 27. |
| DOI: |
10.1038/cr.2012.45 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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