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04 May 2018

Recognition of double-stranded RNA and regulation of interferon pathway by toll-like receptor 10

Suki Lee, principal investigator at HKU-Pasteur Research Pole, and her colleagues at HKU School of Biomedical Sciences and Chinese Academy of Sciences have recently revealed a novel nucleotide sensing receptor and provides new mechanistic insight explaining its role in regulating IFN response in an article for Frontiers in Immunology.

Toll-like receptor (TLR)-10 is the least characterized TLR and still remains an orphan receptor, with only very limited information available regarding its localization, agonist, signaling and function. We have revealed lately that TLR10 is predominantly localized to endosomes and binds dsRNA. We provided different lines of evidences to demonstrate that dsRNA is in fact a ligand for TLR10 sensing and signaling, thereby identifying a previously unrecognized role of TLR10 as a novel nucleotide sensing receptor. We also revealed that TLR10 competes with TLR3 for ligand binding and proposed a model to illustrate the mechanisms for dual functions of TLR10 in the regulation of dsRNA-mediated IFN signaling. This work provides new mechanistic insight explaining the major role of TLR10 in regulating IFN response upon dsRNA stimulation.

As there is increasing evidence suggesting the involvement of TLR10 in different disease pathogenesis. We believe that these new findings not only provide important fundamental insights to the understanding of immunobiology of TLR10, but also bring indispensable importance to further investigate the role and functional relevance of TLR10 in diseases. Modulation of TLR10 signaling may thus provide a unique option to fine-tune fundamental physiological pathways involved in disease pathological conditions.

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