The miR-126-VEGFR2 axis controls the innate response to pathogen-associated nucleic acids
Open accessAbstract
miR-126 is a microRNA expressed predominately by endothelial cells and controls angiogenesis. We found miR-126 was required for the innate response to pathogen-associated nucleic acids and that miR-126-deficient mice had greater susceptibility to infection with pseudotyped HIV. Profiling of miRNA indicated that miR-126 had high and specific expression by plasmacytoid dendritic cells (pDCs). Moreover, miR-126 controlled the survival and function of pDCs and regulated the expression of genes encoding molecules involved in the innate response, including Tlr7, Tlr9 and Nfkb1, as well as Kdr, which encodes the growth factor receptor VEGFR2. Deletion of Kdr in DCs resulted in reduced production of type I interferon, which supports the proposal of a role for VEGFR2 in miR-126 regulation of pDCs. Our studies identify the miR-126-VEGFR2 axis as an important regulator of the innate response that operates through multiscale control of pDCs.
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pDCs express high levels of TLR7 and TLR9 in their endosomes and the cytoplasmic DNA sensor cGAS, enabling detection of viral DNA and single-stranded RNA genomes and production of high amounts of IFN-I upon TLR or cGAS activation.
“pDCs express high levels of TLR7 and TLR9 in their endosomes as well as the cytoplasmic DNA sensor cGAS and are thus well equipped to detect viral DNA and single-stranded RNA genomes and produce high amounts of IFN-I upon TLR or cGAS activation.46,47,48,49”
From TLR9-independent CD8+ T cell responses in hepatic AAV gene transfer through IL-1R1-MyD88 signaling (2024) · cites this paper as [46]
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- Authors
- Agudo, J., Ruzo, A., Tung, N., Salmon, H., Leboeuf, M., Hashimoto, D., Becker, C., Garrett-Sinha, L.-A., Baccarini, A., Merad, M., & Brown, B. D.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Brown, Brian D
- ORCID
- Venue
- Nature Immunology
- Published
- 2013-11-24
- Volume
- 15
- Issue
- 1
- Pages
- 54-62
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC3896265
- OpenAlex
- W2038244683
- Cited by
- 122
- References
- 50
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 2 · 2023: 7 · 2022: 8 · 2021: 13 · 2020: 11 · 2019: 7 · 2018: 10 · 2017: 18 · 2016: 14 · 2015: 14 · 2014: 7 · 2013: 2
- FWCI
- 6.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1dp2dk083052-01)
- National Cancer Institute (CA154947A, R01CA154947)
- National Institute of Allergy and Infectious Diseases (R01AI104848, AI 089987, U19AI089987, AI10008)
- National Institute of Diabetes and Digestive and Kidney Diseases (DP2DK083052)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- miR-126, VEGFR2, plasmacytoid dendritic cells, type I interferon, innate immune response, KDR, TLR7, TLR9, NF-κB, HIV infection, microRNA regulation, dendritic cell homeostasis
- MeSH terms
- Animals, Dendritic Cells, Flow Cytometry, Humans, Immunity, Innate, Mice, Transgenic, Nucleic Acids, Oligodeoxyribonucleotides, Immunoblotting, HIV Infections, Interferon-alpha, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, MicroRNAs, Vascular Endothelial Growth Factor Receptor-2, Toll-Like Receptor 7, Toll-Like Receptor 9, Mice, NF-kappa B p50 Subunit, Transcriptome
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