The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Self-RNA–antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8
Open accessAbstract
Dendritic cell (DC) responses to extracellular self-DNA and self-RNA are prevented by the endosomal seclusion of nucleic acid–recognizing Toll-like receptors (TLRs). In psoriasis, however, plasmacytoid DCs (pDCs) sense self-DNA that is transported to endosomal TLR9 upon forming a complex with the antimicrobial peptide LL37. Whether LL37 also interacts with extracellular self-RNA and how this may contribute to DC activation in psoriasis is not known. Here, we report that LL37 can bind self-RNA released by dying cells, protect it from extracellular degradation, and transport it into endosomal compartments of DCs. In pDC, self-RNA–LL37 complexes activate TLR7 and, like self-DNA–LL37 complexes, trigger the secretion of IFN-α without inducing maturation or the production of IL-6 and TNF-α. In contrast to self-DNA–LL37 complexes, self-RNA–LL37 complexes also trigger the activation of classical myeloid DCs (mDCs). This occurs through TLR8 and leads to the production of TNF-α and IL-6, and the differentiation of mDCs into mature DCs. We also found that self-RNA–LL37 complexes are present in psoriatic skin lesions and are associated with mature mDCs in vivo. Our results demonstrate that the cationic antimicrobial peptide LL37 converts self-RNA into a trigger of TLR7 and TLR8 in human DCs, and provide new insights into the mechanism that drives the auto-inflammatory responses in psoriasis.
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Cites
A Toll-like receptor recognizes bacterial DNA
Hemmi, H., Takeuchi, O., Kawai, T., Kaisho, T., Sato, S., Sanjo, H., Matsumoto, M., Hoshino, K., Wagner, H., Takeda, K., et al. (2000) · Nature · doi:10.1038/35047123 · Cited by 6,491 · cited 1×
“…et al., 2001); TLR7 and TLR8, which recognize guanosineand uridine-rich single-stranded RNA (ssRNA) (Diebold et al., 2004; Heil et al., 2004; Lund et al., 2004); and TLR9, which recognizes the phosphodiester backbone in natural DNA or unmethylated CpG motifs (Hemmi et al., 2000; Haas et al., 2008).”
BackgroundRecognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
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Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response
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Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA
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Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide
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Self-citationPlasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases
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Self-citationA role for human skin–resident T cells in wound healing
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Cited by
The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors
Kawai, T., & Akira, S. (2010) · Nature Immunology · doi:10.1038/ni.1863 · Cited by 9,304
Pattern Recognition Receptors and Inflammation
Takeuchi, O., & Akira, S. (2010) · Cell · doi:10.1016/j.cell.2010.01.022 · Cited by 8,895
Antimicrobial host defence peptides: functions and clinical potential
Mookherjee, N., Anderson, M. A., Haagsman, H. P., & Davidson, D. J. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0058-8 · Cited by 1,502
Human dendritic cell subsets: an update
Collin, M., & Bigley, V. (2018) · Immunology · doi:10.1111/imm.12888 · Cited by 1,301
Nucleic acid recognition by the innate immune system
Barbalat, R., Ewald, S. E., Mouchess, M. L., & Barton, G. M. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101340 · Cited by 577
Metadata
- Authors
- Ganguly, D., Chamilos, G., Lande, R., Gregorio, J., Meller, S., Facchinetti, V., Homey, B., Barrat, F. J., Zal, T., & Gilliet, M.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2009-08-24
- Volume
- 206
- Issue
- 9
- Pages
- 1983-1994
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2100446659
- Cited by
- 740
- References
- 9
- FWCI
- 18.71
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Ganguly, D., Chamilos, G., Lande, R., Gregorio, J., Meller, S., Facchinetti, V., Homey, B., Barrat, F. J., Zal, T., & Gilliet, M. (2009). Self-RNA–antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20090480
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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