MicroRNA Expression Profiles of Human Blood Monocyte-derived Dendritic Cells and Macrophages Reveal miR-511 as Putative Positive Regulator of Toll-like Receptor 4
Open accessAbstract
Dendritic cells (DCs) and macrophages (MFs) are important multifunctional immune cells. Like other cell types, they express hundreds of different microRNAs (miRNAs) that are recently discovered post-transcriptional regulators of gene expression. Here we present updated miRNA expression profiles of monocytes, DCs and MFs. Compared with monocytes, ∼50 miRNAs were found to be differentially expressed in immature and mature DCs or MFs, with major expression changes occurring during the differentiation. Knockdown of DICER1, a protein needed for miRNA biosynthesis, led to lower DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and enhanced CD14 protein levels, confirming the importance of miRNAs in DC differentiation in general. Inhibition of the two most highly up-regulated miRNAs, miR-511 and miR-99b, also resulted in reduced DC-SIGN level. Prediction of miRNA-511 targets revealed a number of genes with known immune functions, of which TLR4 and CD80 were validated using inhibition of miR-511 in DCs and luciferase assays in HEK293 cells. Interestingly, under the cell cycle arrest conditions, miR-511 seems to function as a positive regulator of TLR4. In conclusion, we have identified miR-511 as a novel potent modulator of human immune response. In addition, our data highlight that miRNA influence on gene expression is dependent on the cellular environment.
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miR-1, miR-99b, miR-139-5p, miR-212, miR-218, and miR-511 are overexpressed in macrophages and involved in the TLR signaling pathway.
“Tserel et al. identified miR-1, miR-99b, miR-139-5p, miR-212, miR-218, and miR-511 as overexpressed in macrophages and involved in the toll-like receptor signaling pathway”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [135]
The 'Updated miRNA profile of human DCs and MFs' section reports that miR-99b, miR-212 and miR-511 were highly up-regulated in both dendritic cells and macrophages relative to monocytes, while miR-139-5p, miR-1 and miR-218 had higher expression in macrophages. Table 1 (FOOTNOTES; page unavailable) identifies predicted Toll-like receptor signaling targets for miR-511, and the Discussion examines its possible effect on TLR4. The paper does not establish that all six miRNAs are involved in that pathway. (LLM, conf=0.88)
Experimental — accuracy not yet measuredmiR-511 binds the 3′UTR of TLR4 and upregulates TLR4 in dendritic cells.
“They also confirmed binding of miR-511 with 3′UTR of TLR4, however, resulting in upregulation of TLR4 in dendritic cells [135].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [135]
The results section (page unavailable) reports that TLR4 protein was about twice as high in control-treated differentiating dendritic cells as in cells treated with a miR-511 inhibitor, supporting positive regulation. It identifies predicted miR-511 sites in the TLR4 3′UTR and tests those fragments in luciferase reporters, but does not confirm direct binding. The paper describes miR-511 as a putative regulator, so the citing sentence overstates that part of the evidence. (LLM, conf=0.86)
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- Authors
- Tserel, L., Runnel, T., Kisand, K., Pihlap, M., Bakhoff, L., Kolde, R., Peterson, H., Vilo, J., Peterson, P., & Rebane, A.
- Affiliations
- University of Tartu (EE)
- Corresponding author
- Rebane, Ana
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 286
- Issue
- 30
- Pages
- 26487-26495
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3143613
- OpenAlex
- W2027996995
- Cited by
- 136
- References
- 51
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 13 · 2019: 9 · 2018: 5 · 2017: 10 · 2016: 12 · 2015: 11 · 2014: 20 · 2013: 16 · 2012: 20
- FWCI
- 6.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Sihtasutus Archimedes
- Eesti Teadusfondi
- Hariduse Infotehnoloogia Sihtasutus
- Tartu Ülikool
- European Regional Development Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- microRNA expression profiles, dendritic cells, macrophages, monocytes, miR-99b, TLR4, DC-SIGN, CD14, CD80, DICER1, dendritic cell differentiation, cell cycle arrest, post-transcriptional regulation, immune response
- MeSH terms
- DC-Specific ICAM-3 Grabbing Nonintegrin, Cell Differentiation, Dendritic Cells, Gene Expression Regulation, Humans, Macrophages, Monocytes, Receptors, Cell Surface, Cell Adhesion Molecules, B7-1 Antigen, Lipopolysaccharide Receptors, Gene Expression Profiling, MicroRNAs, Lectins, C-Type, Ribonuclease III, Toll-Like Receptor 4, DEAD-box RNA Helicases, Gene Knockdown Techniques, HEK293 Cells
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