AUTHOR=Lee Suki Man-Yan , Yip Tsz-Fung , Yan Sheng , Jin Dong-Yan , Wei Hong-Li , Guo Rey-Ting , Peiris Joseph Sriyal Malik 

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

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00516

DOI=10.3389/fimmu.2018.00516

ISSN=1664-3224

ABSTRACT=<p>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 <italic>in vitro</italic> 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.</p>