Table 2.
Regulation of type I IFN production by receptor interactions.
| Activating Receptors of Type I IFN Production | ||||
|---|---|---|---|---|
| Regulating Factor | Type of Regulation | Mechanism of Regulation | Model | Ref. |
| CD300a/c | positive | increases IRF7 expression | Human | [89] |
| PDC-TREM | positive | increases the phosphorylation of PI3K, ERK1/2 and IKKα | Mouse | [90] |
| Ly49Q | positive | controls the intracellular trafficking of TLR9/CpG-A containing vesicular compartments | Mouse | [92] |
| Ly49Q | positive | increases IRF7 nuclear translocation and type I IFN gene expression | Mouse | [94] |
| SLAMF9 | positive | supports SpiB expression | Mouse | [95] |
| RAGE | positive | supports transport of extracellular DNA to TLR9 (demonstrated on HEK293T cells) | mouse/human | [99,100] |
| Inhibitory Receptors of Type I IFN Production | ||||
| Regulating Factor | Type of Regulation | Mechanism of Regulation | Model | Ref. |
| BDCA2 | negative | interacts with FcRγ, which activates ITAM-mediated inhibitory signals | human/mouse | [101,102,103,104] |
| ILT7 | negative | interacts with FcRγ (FcεRIγ), which activates ITAM-mediated inhibitory signals | Human | [105] |
| Siglec-H | negative | interacts with DAP12, which activates ITAM-mediated inhibitory signals | Mouse | [106] |
| Siglec-1 | negative | - | Human | [107] |
| LMIR8 | negative | interacts with FcRγ, which activates ITAM-mediated inhibitory signals | Mouse | [108] |
| NKp44 | negative | interacts with DAP12, which activates ITAM-mediated inhibitory signals | Human | [109] |
| LAIR-1 | negative | through its ITIM motif recruits SHP-1 and increases its phosphatase activity (demonstrated on monocytes) | Human | [110,111] |
| DCIR | negative | through its ITIM motif recruits SHP-1 (demonstrated in HL-60 cells) | Mouse | [112,113] |
| PIR-B | negative | through SHP-1 recruitment leads to the dephosphorylation of STAT1/2 | Mouse | [114] |
| PTPRS | negative | - | Human | [115] |
| PTPRF | negative | - | Mouse | [115] |
| EBI2 | negative | through Gαi subunit of the G protein inhibits type I IFN responses | Mouse | [116] |
| CD28 | negative | - | Mouse | [117] |
| TIM-3 | negative | inhibits the trafficking of nucleic acids into endosomes (demonstrated on BM-DCs) | Mouse | [118] |
| Receptors with Distinct Regulatory Roles: Fc Receptors | ||||
| Regulating Factor | Type of Regulation | Mechanism of Regulation | Model | Ref. |
| FcγRIIα+ IgG containing immune complex | positive | supports TLR9 trafficking | Human | [119] |
| FcεRI+ IgE containing immune complex | positive | promotes the delivery of DNA to TLR9 | Human | [120] |
| FcεRI+ free IgE | negative | triggers TNF-α, which reduces TLR9 expression | Human | [121,122] |
| Interactions of Pattern Recognition Receptors | ||||
| Regulating Factor | Type of Regulation | Mechanism of Regulation | Model | Ref. |
| TLR7-TLR9 | negative | TLR7 activation inhibits TLR9-triggered IRF7 expressionand downregulates TLR9 | human/mouse | [123,124] |
| MR-TLR9 | positive | - | Mouse | [125] |
| TLR7-RLR | positive | TLR7 activation induces RLR expression | Human | [40] |
| TLR9-RLR | positive | TLR9 activation induces RLR expression | Human | [40] |
| NLRX1-RLR | negative | - | Human | [126] |
| NLRC5-RLR | negative | - | Human | [126] |
| TLR9-cGAS/STING | negative | cGAS/STING stimulation upregulates SOCS1 and SOCS3 | Human | [127] |
| Adhesion Receptors | ||||
| Regulating Factor | Type of Regulation | Mechanism of Regulation | Model | Ref. |
| LFA-1 | positive | induces TLR7 trafficking from endosomes to lysosomes | Mouse | [128] |
Abbreviations: BDCA2: blood dendritic cells antigen 2; BM-DC: bone marrow-derived dendritic cell; CD: cluster of differentiation; cGAS: cyclic GMP-AMP synthase; DAP12: DNAX activating protein of 12 kDa; DCIR: dendritic cell immunoreceptor; EBI2: Epstein-Barr virus-induced G-protein-coupled receptor 2; ERK1/2: extracellular signal-regulated kinase 1/2; FcRγ: γ subunit of the Fc receptor; FcγRIIα: Fc gamma receptor II alpha; FcεRI: Fc epsilon receptor I; FcεRIγ: γ subunit of the Fc epsilon receptor; Gαi: Gi alpha subunit; IFN: interferon; IgE: immunoglobulin E; IKKα: IκB kinase (IKK) complex α; ILT7: immunoglobulin-like transcript 7; IRF: interferon regulatory factor; ITAM: immunoreceptor tyrosine-based activation motif; ITIM: immunoreceptor tyrosine-based inhibition motif; LAIR-1: leukocyte-associated immunoglobulin-like receptor 1; LFA-1: lymphocyte function-associated antigen 1; LMIR8: leukocyte mono-immunoglobulin-like receptor 8; MR: mannose receptor; mTOR: mammalian target of rapamycin; NKp44: natural killer cell p44-related protein; NLRC5: NOD-like receptor family CARD domain containing 5; NLRX1: nucleotide-binding domain and leucine-rich repeat–containing protein X1; p70S6K: P70 S6 kinase; PDC-TREM: plasmacytoid dendritic cell—triggering receptor expressed on myeloid cells; PI3K: phosphatidylinositol 3-kinase; PIR-B: paired immunoglobulin-like receptor B; PTPRF: Protein tyrosine phosphatase receptor type F; PTPRS: Protein tyrosine phosphatase receptor type S; RAGE: receptor for advanced glycation endproducts; RLR: RIG-I-like receptor; SHP-1: Src homology 2 domain-containing protein tyrosine phosphatase 1; Siglec: sialic acid-binding immunoglobulin-type lectin; SLAMF9: signaling lymphocytic-activating molecule family 9; SOCS: suppressor of cytokine signaling; STAT: signal transducer and activator of transcription; STING: stimulator of IFN genes; TIM-3: T cell immunoglobulin and mucin domain-containing protein 3; TLR: toll-like receptor; TNF: tumor necrosis factor.