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Front Immunol. 2018 Mar 16;9:516. doi: 10.3389/fimmu.2018.00516. eCollection 2018.

Recognition of Double-Stranded RNA and Regulation of Interferon Pathway by Toll-Like Receptor 10.

Author information

1
HKU-Pasteur Research Pole and Center of Influenza Research, Li Ka Shing Faculty of Medicine, School of Public Health, The University of Hong Kong, Pokfulam, Hong Kong.
2
Li Ka Shing Faculty of Medicine, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
3
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.

Abstract

Toll-like receptor (TLR)-10 remains an orphan receptor without well-characterized ligands or functions. Here, we reveal that TLR10 is predominantly localized to endosomes and binds dsRNA in vitro at endosomal pH, suggesting that dsRNA is a ligand of TLR10. Recognition of dsRNA by TLR10 activates recruitment of myeloid differentiation primary response gene 88 for signal transduction and suppression of interferon regulatory factor-7 dependent type I IFN production. We also demonstrate crosstalk between TLR10 and TLR3, as they compete with each other for dsRNA binding. Our results suggest for the first time that dsRNA is a ligand for TLR10 and propose novel dual functions of TLR10 in regulating IFN signaling: first, recognition of dsRNA as a nucleotide-sensing receptor and second, sequestration of dsRNA from TLR3 to inhibit TLR3 signaling in response to dsRNA stimulation.

KEYWORDS:

IFN; TLR10; dsRNA; interferon regulatory factor; ligand sequestration; myeloid differentiation primary response gene 88; nucleotide-sensing receptor; toll-like receptor

PMID:
29616030
PMCID:
PMC5865411
DOI:
10.3389/fimmu.2018.00516
[Indexed for MEDLINE]
Free PMC Article

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