Table 1.
IFNs
| IFNs | Subtype | Cell source | Target cells | Common pathway | Known functions | COVID-19 | Regulated miRNA | Regulatory miRNAs | References |
|---|---|---|---|---|---|---|---|---|---|
| IFN-I | IFN-α | pulmonary epithelial cells, DCs, macrophages | many cell types, B cells, and monocytes | NF-κB, JAK-STAT (MAPK, PI3-kinase) | induces ACE2 as an ISG in human upper airway epithelial cells | reduced the number of viruses, resulting in relief of symptoms, leading to shorter disease duration | miR-130a/301, miR-203, miR-122 | miR-466l, miR-22, miR-122 | 34, 35, 36, 37, 38,41, 42, 43, 44, 45, 46,156, 157, 158,161, 162, 163,241 |
| IFN-β | pulmonary epithelial cells, DCs, macrophages | immune cells (B cells, T cells), monocytes, macrophages, DCs | NF-κB, JAK-STAT (MAPK, PI3-kinase) | effective antiviral action via ISGs | IFN-β-1b administration in severe COVID-19 had positive effects on clinical improvement and duration of hospital stay without serious adverse effects in patients | miR-155, miR-29a, miR-26a, miR-34a, Let-7b, miR-21, miR-122 | miR-146a miR-26a miR-34, Let-7b |
34, 35, 36, 37, 38,41,47, 48, 49, 50, 51, 52, 53, 54,159, 160, 161,164, 165, 166 | |
| IFN-κ | macrophages, monocytes, DCs, keratinocytes | monocytes, dendritic cells | NF-κB, JAK-STAT (MAPK, PI3-kinase) | influence innate immune system cells. Improved symptoms such as cough in patients with asthma | IFN-κ plus TFF2 could significantly enhance clinical improvement | not reported | not reported | 31,34, 35, 36, 37, 38,55, 56, 57 | |
| IFN-δ | porcine blastocysts | not reported | not reported | antiviral and immunomodulatory activity. Lower antiviral activity than IFN-α | not reported | not reported | not reported | 58,59 | |
| IFN-ε | lung, brain, skin tissue, intestinal system, reproductive tissues (Uterus, Cervix, Vagina, Ovary) | macrophages | NF-κB, JAK-STAT (MAPK, PI3-kinase) | mucosal immunity against viral and bacterial infections. Suppression of HIV replication. Protection of reproductive system against viral infections | may be explanation for lower mortality rate in women with SARS-CoV-2 infection than men | not reported | not reported | 34, 35, 36, 37, 38,60, 61, 62, 63, 64, 65, 66, 67, 68 | |
| IFN-τ | bovine blastocysts, endometrial cells | can affect human macrophages | JAK-STAT (bovine) | reduced inflammatory cell infiltration into lung tissue in mouse model of allergy. Antiviral activity. Antiproliferative effects | not reported | bta-miR-204 (bovine endometrial epithelial cells) | not reported | 69, 70, 71,242,243 | |
| IFN-ω | dendritic cells | leukocytes, epithelial cells | NF-κB, JAK-STAT (MAPK, PI3-kinase, P13K/Akt) signaling) | antiviral effects | anti-SARS activity similar to IFN-β. Useful in severe COVID-19 patients with pneumonia | not reported | not reported | 34, 35, 36, 37, 38,72, 73, 74, 75, 76 | |
| IFN-ζ | in mice bronchial epithelial cells, salivary duct cells |
IFN-α/βR-expressing cells | not exactly known (IRF-1 pathway?) | antiviral and immunomodulatory effects | not reported | not reported | not reported | 77,79 | |
| IFN-II | – | bronchial epithelial cells, NK cells, T cells, macrophages | T cells, NK cells | NF-κB, JAK-STAT (MAPK, PI3-kinase) | inhibited acute inflammation (inhibited innate/acquired immunity transition) | expression of IFN tends to be lower in severe COVID-19 than mild cases | miR-29a, miR-155, miR-520b | miR-29, miR-181a | 80, 81, 82, 83,168,243, 244, 245, 246, 247 |
| IFN-III | IFN-λ1 (or IL-29), IFN-λ2 (or IL-28A), IFN-λ3 (or IL-28B), IFN-λ4 | epithelial cells, macrophages, DCs, cytotoxic T cells, NK cells, regulatory T cells | keratinocytes, neutrophils, macrophages, DCs, ECs, respiratory epithelial cells | JAK-STAT (MAPK, PI3-kinase) | reduced systemic inflammation | reduced viral load and inflammatory responses | miR-15a | miR-548, miR-29 | 35,37,84, 85, 86, 87, 88,92,93,169,248, 249, 250, 251, 252 |