let-7 MicroRNAs Regulate Microglial Function and Suppress Glioma Growth through Toll-Like Receptor 7

Alice Buonfiglioli; Ibrahim E. Efe; Dilansu Guneykaya; Andranik Ivanov; Yimin Huang; Elisabeth Orlowski; Christina Krüger; Rudolf A. Deisz; Darko Markovic; Charlotte Flüh; Andrew G. Newman; Ulf C. Schneider; Dieter Beule; Susanne A. Wolf; Omar Dzaye; David H. Gutmann; Marcus Semtner; Helmut Kettenmann; Seija Lehnardt

Cell Reports (Dec 2019)

let-7 MicroRNAs Regulate Microglial Function and Suppress Glioma Growth through Toll-Like Receptor 7

Alice Buonfiglioli,
Ibrahim E. Efe,
Dilansu Guneykaya,
Andranik Ivanov,
Yimin Huang,
Elisabeth Orlowski,
Christina Krüger,
Rudolf A. Deisz,
Darko Markovic,
Charlotte Flüh,
Andrew G. Newman,
Ulf C. Schneider,
Dieter Beule,
Susanne A. Wolf,
Omar Dzaye,
David H. Gutmann,
Marcus Semtner,
Helmut Kettenmann,
Seija Lehnardt

Affiliations

Alice Buonfiglioli: Institute of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Department of Cellular Neurosciences, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany
Ibrahim E. Efe: Department of Cellular Neurosciences, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany; Department of Radiology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Dilansu Guneykaya: Department of Cellular Neurosciences, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany
Andranik Ivanov: Core Unit Bioinformatics, Berlin Institute of Health, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Yimin Huang: Department of Cellular Neurosciences, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany
Elisabeth Orlowski: Department of Cellular Neurosciences, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany
Christina Krüger: Institute of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Rudolf A. Deisz: Institute of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Darko Markovic: Department of Neurosurgery, Helios Clinics, 13125 Berlin, Germany
Charlotte Flüh: Department of Neurosurgery, University Medical Center Schleswig-Holstein (UKSH), 24105 Kiel, Germany
Andrew G. Newman: Institute of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Ulf C. Schneider: Department of Neurosurgery, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Dieter Beule: Core Unit Bioinformatics, Berlin Institute of Health, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
Susanne A. Wolf: Department of Ophthalmology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany
Omar Dzaye: Department of Radiology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
David H. Gutmann: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA
Marcus Semtner: Department of Cellular Neurosciences, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany
Helmut Kettenmann: Department of Cellular Neurosciences, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany; Corresponding author
Seija Lehnardt: Institute of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Department of Neurology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany; Corresponding author

Journal volume & issue: Vol. 29, no. 11
pp. 3460 – 3471.e7

Abstract

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Summary: Microglia express Toll-like receptors (TLRs) that sense pathogen- and host-derived factors, including single-stranded RNA. In the brain, let-7 microRNA (miRNA) family members are abundantly expressed, and some have recently been shown to serve as TLR7 ligands. We investigated whether let-7 miRNA family members differentially control microglia biology in health and disease. We found that a subset of let-7 miRNA family members function as signaling molecules to induce microglial release of inflammatory cytokines, modulate antigen presentation, and attenuate cell migration in a TLR7-dependent manner. The capability of the let-7 miRNAs to control microglial function is sequence specific, mapping to a let-7 UUGU motif. In human and murine glioblastoma/glioma, let-7 miRNAs are differentially expressed and reduce murine GL261 glioma growth in the same sequence-specific fashion through microglial TLR7. Taken together, these data establish let-7 miRNAs as key TLR7 signaling activators that serve to regulate the diverse functions of microglia in health and glioma. : Buonfiglioli et al. elucidate the role of let-7 miRNAs acting as Toll-like receptor (TLR) ligands in the brain. Select let-7 miRNAs function as signaling molecules to modulate diverse microglial functions and glioma growth through TLR7. These data establish let-7 miRNAs as TLR7 signaling activators of microglia in health and glioma. Keywords: glioblastoma, lethal-7, microglia, microRNA, Toll-like receptor 7

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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