Table 4.
Functions, known targets and disease associations of differentially expressed miRNA
| miRNA | Expression in this study | Functions in the immune system † | Specific targets † | Disease associations (Human studies) |
|---|---|---|---|---|
| Both innate and adaptive immune functions | ||||
| miR-29c | Downregulation | Positive regulation of NFκB signaling [26] | TNFAIP3 [26] | Tuberculosis – upregulated [42] |
| Influenza → Upregulation.†† Promotes apoptosis [43] | BCL2L2 [43] | Asthma – downregulated [37] | ||
| miR-31 | Upregulation | Proliferation of myeloid cells [33] | E-selectin [44] | Influenza – downregulated [35] |
| miR-155 | Upregulation | Proliferation of myeloid cells [33] | SHIP1 [33] | Influenza – downregulated [35] |
| Dendritic cell maturation [34,45] | PU.1 [45], SOCS1, CD115, KPC1 [34] | |||
| Positive regulation of TLR signaling [18] | SOCS1 [18] | |||
| Required for dendritic, B and T-cell function [32] | ||||
| let-7d | Upregulation | Promotes Th1 polarization [40] | IL13 [40] | Asthma – downregulated [46] |
| Endotoxin → Upregulation (TLR4 dep.) †† [23] | ||||
| Primarily innate immune functions | ||||
| miR-16 | Upregulation | Negative regulation of inflammation [47] | TNFα [47] | Sepsis – improved survival [48] |
| Positive regulation of NFκB signaling [24] | SMRT [24] | |||
| Negative regulation of NFκB signaling [28] | IKKα [28] | |||
| Endotoxin → Upregulation (TLR4 dep) †† [23] | ||||
| miR-27b | Downregulation | TLR4/NFκB induced nitric oxide production [49] | KSRP [49] | Asthma – downregulated [37] |
| Endotoxin → Upregulation (NFκB dep) †† [50] | ||||
| miR-34b | Downregulation | Endotoxin → Upregulation (TLR4 dep) †† [23] | Asthma – downregulated [37] | |
| miR-34c | Downregulation | Negative regulation of NFκB signaling; DAMPs* → Upregulation [16] | IKKγ [16] | Asthma – downregulated [37] |
| In cord blood monocytes: IFNγ → Upregulation††; Endotoxin → no regulation†† [17] | ||||
| miR-125a | Downregulation | Positive regulation of NFκB signaling [19] | TNFAIP3 [19] | |
| Inhibits CCL5 production [30] | KLF13 [30] | |||
| Macrophage polarization [27,51] | ||||
| miR-125b | Downregulation | Positive regulation of NFκB signaling [19] | TNFAIP3 [19] | CERS** – upregulated [52] |
| Negative regulation of NFκB signaling [18] | MyD88 [18] | |||
| Activates Macrophages [20] | IRF4 [20] | |||
| Modulates dendritic cell differentiation [21] | PRDM1 [21] | |||
| Maintains naïve state in CD4+ T-cells [53] | IFNγ, IL2RB, IL10RA, PRDM1 [53] | |||
| Negative regulation of inflammation [22] | TNFα [22] | |||
| miR-203a | Upregulation | Negative regulation of NFκB signaling [25] | Myd88 [25] | Asthma – upregulated [38] |
| Negative regulation of inflammation [54] | TNFα, IL24 [54] | |||
| No known immune functions | ||||
| miR-429 | Downregulation | |||
†: The functions described are extracted from a literature search April 2014, excluding studies of cancer. This table is not an exhaustive description of all known functions for each miRNA. All studies were carried out in vitro in specific cell lines, and caution should be taken when extrapolating the data to other cells or biological systems, including clinical disease. Specific miRNA functions and mRNA-target verification have in most cases been determined both by removing the miRNA from the biological system and by stimulating the system with the miRNA. miRNA upregulation after cell stimulation has usually been verified by simple qPCR. miRNA responses to cell stimulation have been included in the table if deemed relevant to virus infection or TLR/NFκB signaling.
††: X → Upregulation (Y dep): indicates that in-vitro stimulation of a cell line with molecule or pathogen X causes upregulation of the miRNA, and that this is dependent upon protein Y.
*DAMPs: Damage-associated molecular pattern molecules.
**CERS - Chronic Eosinophilic Rhinosinusitis.