let-7 microRNAs regulate microglial function and suppress glioma growth through Toll-like receptor 7
Autor/innen
- A. Buonfiglioli
- I.E. Efe
- D. Guneykaya
- A. Ivanov
- Y. Huang
- E. Orlowski
- C. Krüger
- R.A. Deisz
- D. Markovic
- C. Flüh
- A.G. Newman
- U.C. Schneider
- D. Beule
- S.A. Wolf
- O. Dzaye
- D.H. Gutmann
- M. Semtner
- H. Kettenmann
- S. Lehnardt
Journal
- Cell Reports
Quellenangabe
- Cell Rep 29 (11): 3460-3471
Zusammenfassung
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.