Table 1.
List of the most prominent miRNAs implicated in the regulation of innate immune cell tolerance.
| MiRNA | Response to TLR signal | Target | Mechanism of action | References |
|---|---|---|---|---|
| miR-146α | Induced | TRAF6, IRAK1, TLR2/4, Notch1 | Targets TLR and TRAF6, IRAK1 in macrophages critical components downstream TLR signaling | (38, 48) |
| miR-146b | Induced | TRAF6 IRAK1 TLR4 | Targets TLR and TRAF6, IRAK1 critical components downstream TLR signaling | (39, 49) |
| miR-155 | Induced | SHIP, SOCS1 CEBP/β FADD, Ripk1 | Inhibits the expression of the negative regulators of TLR signaling, SHIP1 and SOCS1. Promotes TNFα translation. Abrogates expression of anti-inflammatory genes in macrophages | (42–44) |
| MyD88 TAB2, IKKe | Negative regulation of inflammatory cytokine production in macrophages and DCs | (50, 51) | ||
| miR-221 | Induced | TNFα STAT1 STAT2 | Promotes TNFα degradation. Induces tolerance via chromatin remodeling mediated by SWI/SNF (switch/sucrose non-fermentable) and STAT1/2 in macrophages | (3, 52) |
| miR-222 | Induced | STAT1, STAT2 | Induces tolerance via chromatin remodeling mediated by SWI/SNF (switch/sucrose non-fermentable) and STAT1 and 2 in macrophages | (3) |
| miR-132 | Induced | IRAK4 p300 | Responsible for inducing cross tolerance in monocytes/macrophages. Negative effect on the expression of interferon-stimulated genes and antiviral immunity in endothelial cells | (53, 54) |
| miR-21 | Induced | PDCD4 MyD88,IRAK1 IL-12p35 | Negative regulation of TLR4 signaling in monocytes. Inhibits the expression of MyD88 and IRAK1 during viral infection. | (55–58) |
| miR-579 | Induced | TNFα | Negative regulation of TNFα translation in monocytes. | (52) |
| miR-125b | Induced | TNFα MyD88 | Negative regulation of TNFα translation. Negatively regulate viral responses by targeting TLR2/MyD88 signaling in monocytes. | (42, 59) |
| miR-212 | Induced | IRAK4 | Sustained expression is responsible for inducing cross tolerance in monocytes/macrophages. | (54) |
| let-7e | Induced | TLR4 | Negative regulation of TLR4 signaling in macrophages | (43) |
| let-7i | Suppressed | TLR4 | Post-transcription regulation of TLR4 in epithelial cells | (60) |
| miR-124 | Induced | TLR6, MyD88 TRAF6, TNFα | Negatively regulates TLR signaling in BCG infection in macrophages | (61) |
| miR-149 | Suppressed | MyD88 | Represses MyD88 translation in macrophages | (62) |
| miR-203 | Induced | MyD88 | Represses MyD88 translation in macrophages | (63) |
| miR-92a | Suppressed | MAPK4 | Inhibits TLR4 —responses in macrophages | (64) |
| miR-210 | Induced | NFκB1 | Targets NFκB1 upon stimulation in macrophages | (65) |
| miR-9 | Induced | NFκB1 | Negative control of NFκB in monocytes | (66) |
| miR-718 | Induced | PTEN | Down regulates TLR4, IRAK1, and NFκB in a negative feedback loop in macrophages | (67) |
| miR-98 | Suppressed | IL-10 | Targets IL-10 in macrophages | (68) |