Table 3.
Regulation of type I IFN production by extracellular soluble factors.
| Tumor-Derived Factors | ||||
|---|---|---|---|---|
| Regulating Factor | Type of Regulation | Mechanism of Regulation | Model | Ref. |
| Wnt5a | negative | inhibits cytoskeletal rearrangement required for cell activation | human | [159] |
| Wnt5a | negative | upregulates the surface expression of IDO | mouse | [160] |
| VIP | negative | - | human | [163,164] |
| TGFβ | negative | inhibits TLR9 transport to late endosomes and increases its degradation | human | [165] |
| TGFβ in synergy with TNFα | negative | blocks IRF7 expression and nuclear translocation | human | [167,168] |
| TGFβ in synergy with IL-10 | negative | reduces TLR9 mRNA expression | human | [171] |
| IL-10 | negative | - | human | [172] |
| PGE2 in synergy with TGFβ | negative | TGFβ induces smad, whereas PGE2 increases the levels of cAMP | human | [174] |
| PGE2 | negative | suppresses IRF7 mRNA expression | human | [164] |
| HMGB1 | negative | interacts with TIM-3 | mouse | [118] |
| Gal-9 | negative | through interacting with CD44 disrupts the p70S6K/mTOR signalling | human/ mouse |
[178] |
| Biogenic Amines and Steroid Hormones | ||||
| Regulating Factor | Type of Regulation | Mechanism of Regulation | Model | Ref. |
| histamine | negative | acts through H2 and H4 receptors | human | [179,180] |
| histamine, dopamine, serotonin |
negative | binds to CXCR4 and induces its internalization | human | [181] |
| 17β-estradiol | positive | - | mouse | [182,183] |
| 17β-estradiol | positive | increases the expression of IRF5 | human | [184] |
| progesterone | negative | inhibits the TLR9-induced nuclear accumulation of IRF7 (mechanism demonstrated on mouse pDCs) |
human/ mouse |
[185] |
| DMPA | negative | - | mouse | [185] |
| MPA | negative | - | human | [186] |
| DHT | negative | - | human | [187] |
Abbreviations: cAMP: cyclic adenosine monophosphate; CXCR4: C-X-C motif chemokine receptor 4; DHT: dihydrotestosterone; DMPA: depot-medroxyprogesterone acetate; Gal-9: galectin-9; H2: histamine receptor 2; H4: histamine receptor 4; HMGB1: high mobility group box 1 protein; IDO: indoleamine 2,3-dioxygenase; IL: interleukin; IRF: interferon regulatory factor; MPA: medroxyprogesterone acetate; PGE2: prostaglandin E2; TGF-β: transforming growth factor beta; TIM-3: T cell immunoglobulin and mucin domain-containing protein 3; TLR: toll-like receptor; TNF: tumor necrosis factor; VIP: vasoactive intestinal peptide; Wnt5a: wingless-related integration site 5a.