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

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.

SUBMITTER: Lee SM

PROVIDER: S-EPMC5865411 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Lee Suki Man-Yan SM Yip Tsz-Fung TF Yan Sheng S Jin Dong-Yan DY Wei Hong-Li HL Guo Rey-Ting RT Peiris Joseph Sriyal Malik JSM

Frontiers in immunology 20180316

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 <i>in vitro</i> 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 cross ...[more]

PMID: 29616030

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