Table 1.
The regulatory effects of miRNAs on TLR signaling and the TLRs that regulate the miRNAs.
| miRNA | Target/pathway | Cell or tissue type | Function | References | |
|---|---|---|---|---|---|
| The effects of miRNAs on TLR expression and signaling | let-7i | TLR4 | Human cholangiocytes | Regulates TLR4 expression and contributes to immune responses against C. parvum infection | (54) |
| let-7i | TLR4 | Human monocytes | The let-7i mimic inhibits TLR4 expression | (55) | |
| let-7 | TLR4 | Human brain microvascular endothelial cells | Overexpression of let-7i reduces TLR4 expression and inflammation | (56) | |
| let-7/miR-98 | SNAP23/TLR4 | Human non-malignant biliary epithelial cells | The let-7 family reduces SNAP23 expression | (57) | |
| miR-155 | TLR4 signaling | Murine Kupffer cells | Directly regulates expression of IRAK-M, SHIP1, SOCS1, and C/EBPβ | (58) | |
| miR-155 | TLR3 signaling | Murine bone marrow macrophages | MiR-155 expression is dependent on TLR3/TRIF signaling | (59) | |
| miR-155 | Caspase 3 | Murine macrophages | MiR-155–mediated caspase 3 inhibition in LPS-activated macrophages suppresses apoptosis | (60) | |
| miR-155 | TLR3 | Avian macrophages | Inhibits IFN-β production in the TLR3 signaling pathway | (61) | |
| miR-155 | CD1d | Human B cells | Directly targets CD1d upon TLR9 activation | (62) | |
| miR-155 | TLR4 signaling | Murine ischemic cerebral tissue/microglial cells | Promotes TNF-α and IL-1β expression by upregulating TLR4 and downregulating SOCS1 and MyD88 | (63) | |
| miR-155 | MyD88 and SHIP1 | Human primary monocyte-derived macrophages | Regulates downmodulation of MyD88 and SHIP1 expression and inhibits LPS-stimulated TNF-α secretion | (64) | |
| miR-155 | SOCS1 and SHIP1 | PBMCs | Suppresses expression of SOCS1 and SHIP1, which are negative regulators of TLR signaling | (65) | |
| miR-155 | SHIP1 | Murine macrophages | Represses SHIP1 expression and modulates ROS production | (66) | |
| miR-155 | TGF-β and TLR3 signaling | Murine Kupffer cells and macrophages | Blocks the suppressive effect of IL-10 and TGF-β on TLR3 signaling | (67) | |
| miR-155 | TNF-α and MCP1 | Murine microglial cells | MiR-155 expression is induced by alcohol in the cerebellum in a TLR4-dependent manner | (68) | |
| miR-155 | TLR3/4 | Monocyte-derived macrophages | Restores infectivity in poly(I:C)-treated monocyte-derived macrophages | (69) | |
| miR-155 | IRAK-M | Macrophages and PBMCs | Induces TLR7 stimulation and positively regulates IFN-α/β production in PDCs | (70) | |
| miR-155 | SHIP1 | Bone marrow-derived macrophages and PBMCs | IL-10 suppresses miR-155 expression in response to TLR4 stimulation | (71) | |
| miR-155 | TAB2/TLR/IL-1 | PBMCs | Controls the IL-1β pathway | (72) | |
| miR-21 | PDCD4 | Murine macrophages and human monocytes | Inhibits NF-κB activity and promotes IL-10 production | (73) | |
| miR-21 | TLR4/ROS | Human primary lung cancer cells | Downregulation of miR-21 inhibits LPS-induced tumor growth | (74) | |
| miR-21 | TLR4, IRAK3, and CXCL10 | Human monocytes | Overexpression of miR-21 represses downstream transactivation of IL-1β and TNF-α | (75) | |
| TLR signaling may modulate miRNA expression | let-7 | CIS/TLR4 | Human cholangiocytes | Activation of TLR4/MyD88 signaling downregulates miR-98 and let-7 | (76) |
| let-7 | IL-6 and IL-10 | Murine macrophages and human epithelial cells | Repression of let-7 activity relieves the cytokines IL-6 and IL-10 | (77) | |
| let-7 | TLR4 | Murine neuroblastoma cells and macrophages | TLR4 regulates let-7 repression through KSRP | (78) | |
| miR-155 | TLR4 signaling | Murine Kupffer cells | TLR4 signaling regulates miR-155 expression | (79) | |
| miR-155 | SOCS1 | Murine macrophages | Mediates TREM-1–induced effects on TNF-α, IL-1β, and IL-6 | (80) | |
| miR-155 | IL-10 | Murine bone marrow-derived macrophages | Downmodulation of Ets2 expression leads to suppression of miR-155 expression by IL-10 | (81) | |
| miR-155 | TLR2/MyD88 | PBMCs | MiR-155 expression is regulated by HMGB1 in a MyD88-dependent manner | (82) | |
| miR-155 | TLR4 | Bone marrow-derived macrophages | Tenascin-C drives LPS-induced miR-155 expression | (83) | |
| miR-155 | SHIP1 | PBMCs and bone marrow-derived macrophages | F. tularensis infection induces miR-155 expression in a TLR-dependent manner through downregulation of SHIP1 | (84) | |
| miR-155 | SOCS1 | Murine macrophages | Progesterone-based treatment inhibits LPS-induced IL-6 production by decreasing the activity of miR-155 | (85) | |
| miR-21 | PTEN | PDCs | MiR-21–deficient PDCs produce low levels of IFN-α and IFN-γ | (86) | |
| miR-146 | IRAK1 and TRAF6 | Human acute monocytic leukemia cells | LPS induces NF-κB expression through a MyD88-dependent pathway, resulting in upregulation of miR-146 | (87) | |
| miR-146 | TLR4 signaling | Human umbilical vein endothelial cells | Ang-1 triggers upregulation of miR-146b | (88) | |
| The ability of miRNAs to bind to TLRs | miR-21 | TLR7 signaling | Macrophages/microglial cells | In extracellular vesicles, miR-21 can activate TLR7 signaling | (89) |
| let-7b | TLR7 | Murine neurons | Activates TLR7 and causes neurodegeneration | (15) | |
| miR-21 | TLR7/8 signaling | HEK-293 cells and murine macrophages | Functions as a human TLR8 or murine TLR7 ligand | (13) | |
| miR-21 | Hematopoietic cell lines and PBMCs | Functions as an endogenous agonist for TLR8 | (90) | ||
| miR-29a | TLR7/8 signaling | HEK-293 cells and murine macrophages | Functions as a TLR7/8 ligand | (13) | |
| let-7 | TLR7 | Murine macrophages and microglia | Functions as a ligand for murine TLR7 | (15) |
CIS, cytokine-inducible Src homology 2-containing protein; KSRP, KH-type splicing regulatory protein; TREM-1, triggering receptor expressed on myeloid cells 1; ROS, reactive oxygen species; HMGB1, high-mobility group box 1; TGF, transforming growth factor; PDCs, plasmacytoid DCs.