The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Identification of RNA Sequence Motifs Stimulating Sequence-Specific TLR8-Dependent Immune Responses
Abstract
The TLRs 7, 8, and 9 stimulate innate immune responses upon recognizing pathogen nucleic acids. U-rich RNA sequences were recently discovered that stimulate human TLR7/8-mediated or murine TLR7-mediated immune effects. In this study we identified single-stranded RNA sequences containing defined sequence motifs that either preferentially activate human TLR8-mediated as opposed to TLR7- or TLR7/8-mediated immune responses. The identified TLR8 RNA motifs signal via TLR8 and fail to induce IFN-α from TLR7-expressing plasmacytoid dendritic cells but induce the secretion of Th1-like and proinflammatory cytokines from TLR8-expressing immune cells such as monocytes or myeloid dendritic cells. In contrast, RNA sequences containing the TLR7/8 motif signal via TLR7 and TLR8 and stimulate cytokine secretion from both TLR7- and TLR8-positive immunocytes. The TLR8-specific RNA sequences are able to trigger cytokine responses from human and bovine but not from mouse, rat, and porcine immune cells, suggesting that these species lack the capability to respond properly to TLR8 RNA ligands. In summary, we describe two classes of single-stranded TLR7/8 and TLR8 RNA agonists with diverse target cell and species specificities and immune response profiles.
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“Defined synthetic single-stranded phosphorothioate oligoribonucleotides expressing the GUAC motif can strongly induce TNF-α production but not IFN-α through the binding and stimulation of the toll-like receptor 8 on human monocytes and myeloid dendritic cells but not plasmacytoid dendritic cells [75].”
From Differential RNA packaging into small extracellular vesicles by neurons and astrocytes (2021) · cites this paper as [75]
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“Aside from miR-501-3p, the above-mentioned miRNAs contain AU-rich and/or GU-rich sequence motifs required for hTLR7/8 activation [56].”
From Neurodegenerative disease-associated microRNAs acting as signaling molecules modulate CNS neuron structure and viability (2025) · cites this paper as [56]
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Metadata
- Authors
- Forsbach, A., Nemorin, J.-G., Montino, C., Müller, C., Samulowitz, U., Vicari, A. P., Jurk, M., Mutwiri, G. K., Krieg, A. M., Lipford, G. B., & Vollmer, J.
- Affiliations
- Coley Pharmaceutical GmbH , Düsseldorf ,
- Coley Pharmaceutical Ltd. , Ottawa, Ontario ,
- Vaccine and Infectious Disease Organization, University of Saskatchewan , Saskatoon, Saskatchewan ,
- Coley Pharmaceutical Group, Inc. , Wellesley, MA 02481
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-03
- Volume
- 180
- Issue
- 6
- Pages
- 3729-3738
- ISSN
- 0022-1767
- 1550-6606
- Cited by
- 281
- References
- 3
- Language
- en
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