@article{35a52f0ce52c4275ab96c1ef65a85614,
title = "let-7 MicroRNAs Regulate Microglial Function and Suppress Glioma Growth through Toll-Like Receptor 7",
abstract = "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.",
keywords = "Toll-like receptor 7, glioblastoma, lethal-7, microRNA, microglia",
author = "Alice Buonfiglioli and Efe, {Ibrahim E.} and Dilansu Guneykaya and Andranik Ivanov and Yimin Huang and Elisabeth Orlowski and Christina Kr{\"u}ger and Deisz, {Rudolf A.} and Darko Markovic and Charlotte Fl{\"u}h and Newman, {Andrew G.} and Schneider, {Ulf C.} and Dieter Beule and Wolf, {Susanne A.} and Omar Dzaye and Gutmann, {David H.} and Marcus Semtner and Helmut Kettenmann and Seija Lehnardt",
note = "Funding Information: We thank Regina Piske, Maren Wendt, Nadine Scharek, and Michaela Seeger-Zografakis, as well as the Advanced Light Microscopy facility and FACS facility of the Max-Delbrueck-Center for technical assistance. We thank Prof. Dr. Wolfgang Uckert for providing the lentiviral vector. We thank the Lehnardt and Kettenmann labs for helpful discussions. This work was supported by Deutsche Forschungsgemeinschaft (LE 2420/2-1, SFB-TRR167/B3 to S.L), NeuroCure (Exc 257 to A.B. H.K. and S.L.), an Alexander von Humboldt Award (to D.H.G.), Berlin Institute of Health/Einstein Fellowship grant (to D.H.G. and H.K.), Berliner Krebsgesellschaft e.V., the Monika Kutzner Foundation, the BIH-Charit{\'e} Clinician Scientist Program (to O.D.), and the Medical Neuroscience graduate program of Charit{\'e}, Berlin (to A.B.). H.K. and S.L. conceptualized and supervised the study. H.K. S.L. A.B. and D.H.G. wrote the manuscript with input from all other authors. A.B. A.I. A.G.N. C.K. D.B. D.G. D.H.G. E.O. I.E.E. M.S. O.D. S.A.W. and Y.H. carried out the experiments and analyzed and/or discussed data. C.F. D.M. R.A.D. and U.C.S. provided the human biopsies. The authors declare no competing interests. Funding Information: We thank Regina Piske, Maren Wendt, Nadine Scharek, and Michaela Seeger-Zografakis, as well as the Advanced Light Microscopy facility and FACS facility of the Max-Delbrueck-Center for technical assistance. We thank Prof. Dr. Wolfgang Uckert for providing the lentiviral vector. We thank the Lehnardt and Kettenmann labs for helpful discussions. This work was supported by Deutsche Forschungsgemeinschaft ( LE 2420/2-1 , SFB-TRR167/B3 to S.L), NeuroCure ( Exc 257 to A.B., H.K., and S.L.), an Alexander von Humboldt Award (to D.H.G.), Berlin Institute of Health/Einstein Fellowship grant (to D.H.G. and H.K.), Berliner Krebsgesellschaft e.V. , the Monika Kutzner Foundation , the BIH-Charit{\'e} Clinician Scientist Program (to O.D.), and the Medical Neuroscience graduate program of Charit{\'e} , Berlin (to A.B.). Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = dec,
day = "10",
doi = "10.1016/j.celrep.2019.11.029",
language = "English",
volume = "29",
pages = "3460--3471.e7",
journal = "Cell Reports",
issn = "2211-1247",
number = "11",
}