Schematic presentation of select miRNAs that regulate toll-like receptor signaling pathways. During innate immune response, toll-like receptors (TLRs) are activated by various pathogens and initiate signaling transduction to induce the production of type I interferons (IFNs) and other inflammatory cytokines. miRNAs exert pronounced control of the pathway activation at multiple levels to ensure the generation of proper immune response. The miRNAs preferentially target the common signaling components and transcription factors, but also directly act on receptors and cytokine mRNAs. In most cases, decreases in the concentrations of miRNA target proteins achieve effective negative regulation and therefore avoid detrimental immune activation. However, if the target protein itself is a negative regulator (IL-1 receptor-associated kinase (IRAK)-M, suppressor of cytokine signaling-1 (SOCS1), SH2 domain-containing inositol phosphatase-1 (SHIP1)), miRNA-mediated regulation will facilitate TLR signaling and the production of inflammatory cytokines. ERK, extracellular signal-regulated kinase; IFR, interferon regulatory factor; IKK, I-kappa-B kinase; MAL, MyD88 adapter-like; MAPK, mitogen-activated protein kinase; TAB, TAK1-binding protein; TAK, transforming growth factor-beta activated kinase; TBK, TANK-binding kinase; TRAM, TRIF-related adapter molecule; TRAF, TNF receptor-associated factor; TRIF, TIR domain containing adaptor inducing IFNβ.
Luo et al. Arthritis Research & Therapy 2013 15:210 doi:10.1186/ar4194