Extracellular microRNAs initiate immunostimulation via activating toll-like receptor signaling pathways
Tóm tắt
Since the discovery of the stability of extracellular microRNAs (miRNAs) in plasma and other body fluids about a decade ago, an increasing body of literature has addressed the function of extracellular miRNAs as novel regulators of gene expression. Although many of these studies have demonstrated that extracellular miRNAs modulate the target genes of recipient cells in a conventional base-pairing manner after exosome-mediated secretion and uptake of miRNAs, recent studies have shown that extracellular miRNAs can also play an unconventional role by rapidly modulating innate immunity and neuron excitation via directly binding to Toll-like receptors (TLRs). In this review, we will summarize the literature incremented from studying the direct activation of TLR signaling pathways by miRNAs and miRNA-like fragments in modulating immune responses.
Tài liệu tham khảo
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.
Ambros V. The functions of animal microRNAs. Nature. 2004;431:350–5.
Zhang L, et al. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Res. 2012;22:107–26.
Zhang Y, et al. Microvesicle-mediated delivery of transforming growth factor beta1 siRNA for the suppression of tumor growth in mice. Biomaterials. 2014;35:4390–400.
Zhang Y, et al. Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol Cell. 2010;39:133–44.
Chen X, Liang H, Zhang J, Zen K, Zhang CY. Secreted microRNAs: a new form of intercellular communication. Trends Cell Biol. 2012;22:125–32.
Ranganathan P, et al. Serum miR-29a is upregulated in acute graft-versus-host disease and activates dendritic cells through TLR binding. J Immunol. 2017;198:2500–12.
Lehmann SM, et al. An unconventional role for miRNA: let-7 activates toll-like receptor 7 and causes neurodegeneration. Nat Neurosci. 2012;15:827–35.
Sarvestani ST, et al. Sequence-dependent off-target inhibition of TLR7/8 sensing by synthetic microRNA inhibitors. Nucleic Acids Res. 2015;43:1177–88.
Takeda K, Kaisho T, Akira S. Toll-like receptors. Annu Rev Immunol. 2003;21:335–76.
Blasius AL, et al. Slc15a4, AP-3, and Hermansky-Pudlak syndrome proteins are required for toll-like receptor signaling in plasmacytoid dendritic cells. Proc Natl Acad Sci U S A. 2010;107:19973–8.
Dowling JK, Mansell A. Toll-like receptors: the swiss army knife of immunity and vaccine development. Clin Transl Immunology. 2016;5:e85.
Ramirez-Ortiz ZG, et al. The receptor TREML4 amplifies TLR7-mediated signaling during antiviral responses and autoimmunity. Nat Immunol. 2015;16:495–504.
Kariko K, Bhuyan P, Capodici J, Weissman D. Small interfering RNAs mediate sequence-independent gene suppression and induce immune activation by signaling through toll-like receptor 3. J Immunol. 2004;172:6545–9.
Kleinman ME, et al. Sequence- and target-independent angiogenesis suppression by siRNA via TLR3. Nature. 2008;452:591–7.
Heil F, et al. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science. 2004;303:1526–9.
Fabbri M, et al. MicroRNAs bind to toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci U S A. 2012;109:E2110–6.
He WA, et al. Microvesicles containing miRNAs promote muscle cell death in cancer cachexia via TLR7. Proc Natl Acad Sci U S A. 2014;111:4525–9.
Park CK, et al. Extracellular microRNAs activate nociceptor neurons to elicit pain via TLR7 and TRPA1. Neuron. 2014;82:47–54.
Feng Y, et al. Extracellular MicroRNAs induce potent innate immune responses via TLR7/MyD88-dependent mechanisms. J Immunol. 2017;199:2106–17.
Kim SJ, et al. Identification of a novel toll-like receptor 7 endogenous ligand in rheumatoid arthritis synovial fluid that can provoke arthritic joint inflammation. Arthritis Rheumatol. 2016;68:1099–110.
Yelamanchili SV, et al. MiR-21 in extracellular vesicles leads to neurotoxicity via TLR7 signaling in SIV neurological disease. PLoS Pathog. 2015;11:e1005032.
Liu HY, Huang CM, Hung YF, Hsueh YP. The microRNAs Let7c and miR21 are recognized by neuronal toll-like receptor 7 to restrict dendritic growth of neurons. Exp Neurol. 2015;269:202–12.
Salama A, et al. MicroRNA-29b modulates innate and antigen-specific immune responses in mouse models of autoimmunity. PLoS One. 2014;9:e106153.
Karrich JJ, et al. MicroRNA-146a regulates survival and maturation of human plasmacytoid dendritic cells. Blood. 2013;122:3001–9.
Hornung V, et al. Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat Med. 2005;11:263–70.
Sioud M. Induction of inflammatory cytokines and interferon responses by double-stranded and single-stranded siRNAs is sequence-dependent and requires endosomal localization. J Mol Biol. 2005;348:1079–90.
Forsbach A, et al. Identification of RNA sequence motifs stimulating sequence-specific TLR8-dependent immune responses. J Immunol. 2008;180:3729–38.
Diebold SS, et al. Nucleic acid agonists for toll-like receptor 7 are defined by the presence of uridine ribonucleotides. Eur J Immunol. 2006;36:3256–67.
Huang Z, et al. Targeted delivery of let-7b to reprogramme tumor-associated macrophages and tumor infiltrating dendritic cells for tumor rejection. Biomaterials. 2016;90:72–84.
Judge AD, et al. Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nat Biotechnol. 2005;23:457–62.
Peacock H, et al. Nucleobase and ribose modifications control immunostimulation by a microRNA-122-mimetic RNA. J Am Chem Soc. 2011;133:9200–3.
Zhou Z, et al. Honeysuckle-encoded atypical microRNA2911 directly targets influenza a viruses. Cell Res. 2015;25:39–49.
Landais I, et al. Human cytomegalovirus miR-UL112-3p targets TLR2 and modulates the TLR2/IRAK1/NFkappaB signaling pathway. PLoS Pathog. 2015;11:e1004881.
Chen Y, et al. HCV-induced miR-21 contributes to evasion of host immune system by targeting MyD88 and IRAK1. PLoS Pathog. 2013;9:e1003248.
Lukasik A, Zielenkiewicz P. Plant MicroRNAs-novel players in natural medicine? Int J Mol Sci. 2016;18(1).
Cavalieri D, et al. Plant microRNAs as novel immunomodulatory agents. Sci Rep. 2016;6:25761.
Sampey GC, et al. Exosomes from HIV-1-infected cells stimulate production of pro-inflammatory cytokines through trans-activating response (TAR) RNA. J Biol Chem. 2016;291:1251–66.
Gu H, et al. Salmonella produce microRNA-like RNA fragment Sal-1 in the infected cells to facilitate intracellular survival. Sci Rep. 2017;7:2392.
