Next-generation sequencing of microRNAs uncovers expression signatures in polarized macrophages
Abstract
microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at a posttranscriptional level and play a crucial role in the development of cells of the immune system. Macrophages are essential for generating inflammatory reactions upon tissue damage and encountering of invading pathogens, yet modulation of their immune responses is critical for maintaining tissue homeostasis. Macrophages can present different phenotypes, depending on the cytokine environment they encounter in the affected tissues. In this study, we have identified expression signatures of miRNAs that are differentially regulated during maturation of monocytes and polarization of macrophages by cytokines. We present a comprehensive characterization of miRNA expression in human monocytes and M1, M2a, and M2c polarized macrophages, using next-generation sequencing. Furthermore, we show that miRNA expression signatures are closely related to the various immune functions of polarized macrophages and therefore are involved in shaping the diverse phenotypes of these cells. The miRNAs identified here serve as markers for identification of inflammatory macrophages involved in the development of immune responses. Our findings contribute to understanding the role of miRNAs in determining the macrophage function in healthy and diseased tissues.
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Cobos Jiménez et al. found that expression of miR-34a-5p, miR-106-3p, miR-132-3p, miR-335-5p, miR-362-3p, and miR-424-5p was upregulated in macrophages compared with monocytes.
“Expression of miR-34a-5p, miR-106-3p, miR-132-3p, miR-335-5p, miR-362-3p, and miR-424-5p was upregulated in macrophages compared with monocytes.”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [196]
miR-500a-5p and miR-502-3p were upregulated in M2a macrophages; miR-21-5p, miR-22-3p, and miR146b-5p were upregulated, and miR-339-3p was downregulated in M2c cells.
“miR-500a-5p and miR-502–3p were upregulated in M2a macrophages; miR-21-5p, miR-22-3p, and miR146b-5p were upregulated, and miR-339-3p was downregulated in M2c cells.”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [196]
miR-145-5p was uniquely upregulated in M1, miR-181b-5p was uniquely downregulated in M2a, and miR-200a-3p was exclusively downregulated in M2c macrophages.
“MiR-145-5p was uniquely upregulated in M1, whereas miR-181b-5p was uniquely downregulated in M2a cells, and miR-200a-3p was exclusively downregulated in M2c macrophages.”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [196]
miR-146a-5p, miR-193a-5p, and miR-29b-3p were upregulated, and miR-629-5p was downregulated in M1 cells.
“MiR-146a-5p, miR-193a-5p, and miR-29b-3p were upregulated, and miR-629-5p was downregulated in M1 cells.”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [196]
M1 macrophages present high expression of miR-146a-5p, miR-29b-3p, and miR-147b, and low expression of miR-221-3p.
“M1 macrophages present high expression of miR-146a-5p, miR-29b-3p, and miR-147b, and low expression of miR-221-3p.”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [196]
M2c macrophages express high levels of miR-125b-5p, miR-125a-5p, and miR-99b and uniquely low levels of miR-200a-3p.
“M2c macrophages express high levels of miR-125b-5p, miR-125a-5p, and miR-99b and uniquely low levels of miR-200a-3p [196].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [196]
miR-221-3p, miR-222-3p, and miR-511 were highly expressed in M2a macrophages.
“MiR-221-3p, miR-222-3p, and miR-511 were highly expressed in M2a macrophages.”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [196]
M2a macrophages display high levels of miR-193b-3p and miR-511, and low expression of miR-181a-5p and miR-181b-5p.
“M2a macrophages display high levels of miR-193b-3p and miR-511, and low expression of miR-181a-5p and miR-181b-5p.”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [196]
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- Authors
- Cobos Jiménez, V., Bradley, E. J., Willemsen, A. M., van Kampen, A. H. C., Baas, F., & Kootstra, N. A.
- Affiliations
- Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands;
- Amsterdam UMC Location University of Amsterdam (NL)
- Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands; and
- Corresponding author
- Kootstra, Neeltje A.
- Venue
- Physiological Genomics
- Publisher
- American Physiological Society
- Published
- 2014-02-01
- Volume
- 46
- Issue
- 3
- Pages
- 91-103
- ISSN
- 1094-8341 (ISSN-L)
- 1531-2267
- OpenAlex
- W2162762911
- Semantic Scholar
- 34af06ad211be134cc169644e3d037e563fc176a
- Cited by
- 103
- References
- 60
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 7 · 2023: 12 · 2022: 7 · 2021: 14 · 2020: 14 · 2019: 11 · 2018: 6 · 2017: 7 · 2016: 13 · 2015: 3 · 2014: 5
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Physiological Genomics (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- UvA-DARE (University of Amsterdam) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- microRNA, macrophage polarization, monocyte differentiation, M1 macrophages, M2 macrophages, microRNA signature, cytokine regulation, post-transcriptional regulation, inflammatory macrophages, macrophage phenotype
- MeSH terms
- Cell Differentiation, Gene Expression Regulation, Homeostasis, Humans, Immune System, Inflammation, Macrophages, Monocytes, Phenotype, RNA Processing, Post-Transcriptional, Transcription, Genetic, Cytokines, Sequence Analysis, RNA, Gene Expression Profiling, MicroRNAs, High-Throughput Nucleotide Sequencing
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