{"gene":"LILRA4","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":2006,"finding":"ILT7 (LILRA4) associates with the signal adapter protein FcεRIγ to form a receptor complex on human plasmacytoid dendritic cells. Cross-linking of ILT7 results in phosphorylation of Src family kinases and Syk kinase and induces calcium influx, blocked by Src family and Syk kinase inhibitors, indicating ITAM-mediated signaling. ILT7 cross-linking on CpG- or influenza virus-stimulated pDCs inhibits transcription and secretion of type I interferon and other cytokines.","method":"Co-immunoprecipitation of ILT7-FcεRIγ complex; anti-ILT7 cross-linking assay with kinase inhibitors; calcium flux measurement; cytokine ELISA from primary pDCs","journal":"The Journal of experimental medicine","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal functional assays with multiple orthogonal methods (co-IP, kinase phosphorylation, calcium flux, cytokine secretion) in primary pDCs, replicated across subsequent studies","pmids":["16735691"],"is_preprint":false},{"year":2009,"finding":"BST2 (CD317) is a direct ligand of ILT7 (LILRA4). BST2 directly binds purified ILT7 protein, initiates signaling via the ILT7-FcεRIγ complex, and strongly inhibits production of type I IFN and proinflammatory cytokines by pDCs. BST2, readily induced by IFN and proinflammatory cytokines, modulates pDC IFN responses through ILT7 in a negative feedback manner.","method":"Ligand identification via ILT7-reporter cell screen; direct binding assay with purified ILT7 protein and BST2; cytokine inhibition assay with primary pDCs","journal":"The Journal of experimental medicine","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — direct binding with purified proteins, functional reporter assay, and cytokine readout in primary cells; independently replicated across multiple subsequent studies","pmids":["19564354"],"is_preprint":false},{"year":2007,"finding":"ILT7 surface expression on pDCs requires association with the FcεRIγ adaptor molecule. ILT7 is down-regulated when pDCs mature in response to viral or bacterial stimulation. Distinct anti-ILT7 monoclonal antibodies have opposing effects: one suppresses type I IFN production in response to CpG while another up-regulates it.","method":"SAGE library screening; surface expression analysis; functional antibody cross-linking assays with CpG stimulation","journal":"International immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — SAGE expression profiling plus functional antibody cross-linking assays in primary pDCs, single lab","pmids":["18048391"],"is_preprint":false},{"year":2010,"finding":"ILT7 (LILRA4) couples with FcεRIγ signaling adapter to activate a prominent ITAM-mediated signaling pathway in pDCs. ILT7 protein directly binds BST2 protein expressed on IFN-pre-exposed cells or cancer cell surfaces, and this interaction negatively regulates pDC TLR7/9-mediated IFN responses during viral infection.","method":"Review integrating direct binding studies and functional signaling assays from primary experiments described in source papers","journal":"Immunological reviews","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — review synthesizing prior direct binding and functional assays; no new primary data but consolidates established findings","pmids":["20193018"],"is_preprint":false},{"year":2013,"finding":"ILT7 cross-linking suppresses pDC type I IFN production in PBMCs treated with TLR7/9 ligands or HIV, but BST2 blockade does not affect IFN-I responses even when BST2 upregulation is further boosted. ILT7 expression decreases spontaneously in pDCs upon in vitro culture correlating with pDC differentiation. BST2-mediated ILT7 cross-linking may act as a homeostatic regulatory mechanism on immature circulating pDCs rather than a negative feedback for activated mature pDCs.","method":"ILT7 cross-linking antibody treatment of PBMCs; BST2 blocking antibody; flow cytometry; cytokine measurement; HIV stimulation assay","journal":"Journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional cross-linking and blocking assays in primary human PBMCs, single lab, multiple conditions tested","pmids":["23401591"],"is_preprint":false},{"year":2014,"finding":"ILT7 cross-linking on TLR7/9-stimulated pDCs mitigates upregulation of CCR7 and enhances upregulation of β7 integrin, partially reduces CD40 expression but further enhances CD86. pDCs stimulated with TLR9 ligand in the presence of ILT7 cross-linking retain ability to induce T cell proliferation and activation, suggesting ILT7 cross-linking favors differentiation of immature pDCs into antigen-presenting cells rather than IFN-producing cells.","method":"ILT7 cross-linking in PBMC cultures; flow cytometry for surface markers (CCR7, β7, CD40, CD80, CD86); pDC-T cell co-culture with SEB stimulation; T cell proliferation assay","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional cross-linking assays with multiple surface marker readouts and T cell co-culture functional readout, single lab","pmids":["24586760"],"is_preprint":false},{"year":2015,"finding":"HIV-1 Vpu suppresses TLR7-mediated IFN-I production by pDCs through a mechanism relying on BST2-ILT7 interaction. While Vpu downregulates surface BST2 to counteract viral restriction, it also re-locates remaining BST2 molecules outside viral assembly sites where they remain free to bind and activate ILT7 upon cell-to-cell contact, thereby suppressing pDC antiviral responses.","method":"Cell-to-cell contact assay between HIV-producing T cells and pDCs; Vpu mutant constructs; IFN-I production measurement; BST2 surface localization imaging; ILT7 cross-linking functional assay","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (mutant constructs, cell contact assays, localization imaging, functional cytokine readout) establishing mechanism, single rigorous lab study","pmids":["26172439"],"is_preprint":false},{"year":2016,"finding":"Syk kinase plays a dual role in pDC signaling: it positively regulates TLR7/9-mediated IFN-α production and also mediates inhibitory regulatory receptor (ILT7 and BDCA-2) signaling that suppresses TLR-induced IFN production. A Syk inhibitor at concentrations insufficient to block TLR7/9 signaling still released the IFN-α block triggered via ILT7 pathway, partially restoring pDC IFN production.","method":"Pharmacological Syk inhibition (AB8779) in primary pDCs and GEN2.2 cell line; TLR7/9 agonist stimulation; ILT7 cross-linking; IFN-α/cytokine measurement; phosphorylation kinetics analysis (Y352, Y525/526)","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — pharmacological targeting with specific inhibitor, differential phosphorylation kinetics, multiple cell systems tested, single lab","pmids":["27258042"],"is_preprint":false},{"year":2016,"finding":"HIV-1 group O Nef, unlike HIV-1 group M Vpu, does not efficiently displace short BST2 from viral assembly sites and consequently impairs BST2 ability to activate ILT7 signaling to suppress pDC IFN-I responses during sensing of infected cells.","method":"Comparison of O-Nef vs M-Vpu BST2 counteraction; cell-to-cell sensing assay with pDC-containing PBMCs; IFN-I measurement; BST2 surface localization analysis","journal":"Journal of virology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — comparative viral protein functional assay with pDC IFN readout and localization analysis, single lab","pmids":["27581991"],"is_preprint":false},{"year":2018,"finding":"ILT7 (BDCA-2 and ILT7) cross-linking activates a BCR-like signaling pathway that inhibits TLR9-mediated type I IFN production through the MEK1/2-ERK-c-FOS signaling axis in pDCs. MEK1/2 inhibitors potentiated TLR9-mediated IFN-I production and partially restored IFN-α production blocked by ILT7 engagement, correlating with abrogation of MEK1/2-ERK-c-FOS signaling.","method":"ILT7/BDCA-2 mAb cross-linking; BST2-expressing cell stimulation; MEK1/2 inhibitors (PD0325901, U0126); c-FOS expression and phosphorylation analysis; IFN-I cytokine measurement in GEN2.2 cells and primary pDCs","journal":"Frontiers in immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — pharmacological and genetic pathway dissection with multiple inhibitors and downstream marker readouts in two cell systems, single lab","pmids":["29535732"],"is_preprint":false},{"year":2019,"finding":"Structurally distinct regions of the BST2 ectodomain govern ILT7 activation differently: the coiled-coil region contains a newly defined ILT7-binding surface, while the N-terminal region suppresses ILT7 activation. A stable BST2 homodimer binds to ILT7, but post-binding events associated with BST2 coiled-coil plasticity are required to trigger receptor signaling. BST2 with unstable or rigid coiled-coil fails to activate ILT7, whereas N-terminal region substitutions enhance activation.","method":"Biophysical binding studies; two functional ILT7 activation assays; BST2 domain mutagenesis; coiled-coil stability analysis; homodimer binding assessment","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — mutagenesis combined with biophysical binding studies and two orthogonal functional activation assays defining structural mechanism; rigorous single-paper study","pmids":["31118237"],"is_preprint":false},{"year":2009,"finding":"ILT7 ligand (identified as BST2) is expressed on all tested human cancer cell lines and on noncancerous cells exposed to IFN-α, IFN-β, IFN-γ, TNF-α, IL-1β, TGF-β, LPS, or imiquimod. High ILT7L-expressing cancer cells inhibit IFN-α and TNF-α production by CpG-stimulated pDCs. NF-κB and mTOR signaling pathways are involved in regulating ILT7L expression on cancer cells.","method":"ILT7-GFP reporter cell system to detect ILT7 ligand; cytokine stimulation assays; pharmacological inhibition of NF-κB and mTOR; IFN-α/TNF-α measurement by ELISA","journal":"Clinical cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional reporter assay system plus pharmacological pathway analysis, single lab, multiple orthogonal readouts","pmids":["19723650"],"is_preprint":false},{"year":2002,"finding":"ILT7 transcript is selectively expressed in human plasmacytoid dendritic cells compared to monocyte-derived dendritic cells, identified by cDNA subtractive hybridization.","method":"cDNA subtractive hybridization comparing pDCs vs monocyte-derived DCs","journal":"Blood","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — discovery of pDC-selective expression by subtractive hybridization, replicated in subsequent studies","pmids":["12384430"],"is_preprint":false},{"year":2024,"finding":"BST2-ILT7 ligand-receptor-mediated cellular interactions are manipulated by immunoglobin treatment in fulminant myocarditis, with Bst2-ILT7 interactions confirmed in vivo in a coxsackievirus B3 mouse model.","method":"Single-cell RNA sequencing of cardiac CD45+ cells; in vivo immunoglobin treatment; coxsackievirus B3 mouse FM model; ligand-receptor interaction analysis","journal":"British journal of pharmacology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — ligand-receptor interaction confirmed in vivo but mechanistic detail is limited in the abstract; single lab, single model","pmids":["39442535"],"is_preprint":false}],"current_model":"LILRA4 (ILT7) is a plasmacytoid dendritic cell-specific activating receptor that forms a complex with the FcεRIγ signaling adapter; upon engagement by its ligand BST2 (CD317), ILT7 triggers ITAM-mediated phosphorylation of Src family kinases and Syk, inducing calcium influx and downstream MEK1/2-ERK-c-FOS signaling, which collectively inhibits TLR7/9-induced type I interferon and proinflammatory cytokine production by pDCs; BST2 engages ILT7 through its coiled-coil ectodomain as a stable homodimer requiring coiled-coil conformational plasticity for receptor activation, while the BST2 N-terminal region suppresses activation, establishing a structural negative-feedback mechanism that limits pDC IFN responses after viral infection or IFN exposure."},"narrative":{"mechanistic_narrative":"LILRA4 (ILT7) is a plasmacytoid dendritic cell (pDC)-selective activating receptor that acts as a negative regulator of type I interferon responses [PMID:16735691, PMID:12384430]. It lacks intrinsic signaling motifs and instead pairs with the ITAM-bearing adaptor FcεRIγ, an association required for its surface expression; cross-linking of the ILT7–FcεRIγ complex drives phosphorylation of Src-family kinases and Syk, calcium influx, and downstream MEK1/2–ERK–c-FOS signaling that suppresses TLR7/9-induced type I IFN and proinflammatory cytokine production [PMID:16735691, PMID:18048391, PMID:29535732]. Syk occupies a pivotal node, since it both promotes TLR-driven IFN-α and transmits the inhibitory ILT7 signal [PMID:27258042]. The physiological ligand is BST2 (CD317), which binds purified ILT7 directly and engages it as a stable homodimer through a coiled-coil ectodomain surface, with coiled-coil conformational plasticity required for receptor triggering and the BST2 N-terminal region acting to suppress activation—establishing a structural negative-feedback loop in which IFN- and cytokine-induced BST2 restrains pDC IFN output [PMID:19564354, PMID:31118237, PMID:19723650]. This axis is exploited during HIV-1 infection: HIV-1 Vpu relocates BST2 away from viral assembly sites so it remains free to engage and activate ILT7 during cell-to-cell contact, dampening pDC antiviral IFN, a function not efficiently performed by HIV-1 group O Nef [PMID:26172439, PMID:27581991].","teleology":[{"year":2002,"claim":"Establishing that ILT7 is a pDC-restricted gene defined the cell type in which its receptor function would later be interpreted.","evidence":"cDNA subtractive hybridization comparing pDCs to monocyte-derived DCs","pmids":["12384430"],"confidence":"Medium","gaps":["Expression pattern alone did not address receptor function","No ligand or signaling partner identified at this stage"]},{"year":2006,"claim":"The discovery that ILT7 partners with FcεRIγ and triggers Src/Syk-dependent calcium flux to suppress IFN answered how a receptor with no signaling motif regulates pDCs.","evidence":"Co-IP of the ILT7–FcεRIγ complex, anti-ILT7 cross-linking with kinase inhibitors, calcium flux, and cytokine ELISA in primary pDCs","pmids":["16735691"],"confidence":"High","gaps":["The natural ligand was not yet identified","Downstream effectors beyond proximal Src/Syk kinases unresolved"]},{"year":2007,"claim":"Showing that FcεRIγ association is required for ILT7 surface expression and that distinct antibodies have opposing effects clarified the receptor's assembly and dynamic regulation.","evidence":"SAGE screening, surface expression analysis, and functional antibody cross-linking with CpG stimulation in primary pDCs","pmids":["18048391"],"confidence":"Medium","gaps":["Molecular basis for opposing antibody effects not defined","Single-lab functional data"]},{"year":2009,"claim":"Identifying BST2 as the direct ligand defined a negative-feedback circuit, since BST2 is induced by IFN and cytokines and then activates ILT7 to shut down pDC IFN.","evidence":"ILT7-reporter ligand screen, direct binding with purified ILT7 and BST2, and cytokine inhibition in primary pDCs; complemented by reporter-based detection of BST2 on cancer cells and IFN/cytokine-exposed cells","pmids":["19564354","19723650"],"confidence":"High","gaps":["Structural basis of BST2–ILT7 binding not yet defined","Whether feedback operates on immature versus mature pDCs unresolved"]},{"year":2013,"claim":"Testing BST2 blockade and culture-induced ILT7 loss reframed the BST2-ILT7 axis as a homeostatic control on immature circulating pDCs rather than a feedback brake on activated pDCs.","evidence":"ILT7 cross-linking and BST2 blocking antibodies in primary human PBMCs with TLR7/9 ligands and HIV stimulation, flow cytometry, cytokine measurement","pmids":["23401591"],"confidence":"Medium","gaps":["BST2 blockade failing to alter IFN-I leaves the in vivo dominance of the axis unclear","Single-lab observation"]},{"year":2014,"claim":"Demonstrating that ILT7 engagement reshapes pDC surface markers and preserves T-cell stimulatory capacity established that the receptor biases differentiation toward antigen presentation rather than IFN production.","evidence":"ILT7 cross-linking in PBMC cultures with surface-marker flow cytometry and pDC–T cell co-culture proliferation assays","pmids":["24586760"],"confidence":"Medium","gaps":["Signaling link between ILT7 and the differentiation phenotype not mapped","In vivo relevance untested"]},{"year":2015,"claim":"Showing that HIV-1 Vpu relocates BST2 to keep it free to activate ILT7 explained how the virus co-opts this inhibitory axis to suppress pDC antiviral IFN.","evidence":"Cell-to-cell contact assays between HIV-producing T cells and pDCs, Vpu mutants, BST2 surface localization imaging, and ILT7 cross-linking functional readout","pmids":["26172439"],"confidence":"High","gaps":["Quantitative contribution of this axis to overall HIV immune evasion not established"]},{"year":2016,"claim":"Defining Syk's dual role and the MEK1/2-ERK-c-FOS axis, together with comparative viral protein analysis, resolved the downstream signaling cascade and showed it is differentially exploited across HIV lineages.","evidence":"Pharmacological Syk inhibition and phosphorylation kinetics in pDCs and GEN2.2 cells; comparative O-Nef versus M-Vpu BST2-relocation and pDC IFN sensing assays","pmids":["27258042","27581991"],"confidence":"Medium","gaps":["How Syk discriminates activating TLR versus inhibitory ILT7 signals not resolved","Single-lab pharmacological dissection"]},{"year":2018,"claim":"Mapping the inhibitory pathway to a BCR-like MEK1/2-ERK-c-FOS cascade identified the specific effector module through which ILT7 suppresses TLR9-driven IFN.","evidence":"ILT7/BDCA-2 cross-linking with MEK1/2 inhibitors, c-FOS expression/phosphorylation, and IFN-I measurement in GEN2.2 cells and primary pDCs","pmids":["29535732"],"confidence":"Medium","gaps":["Transcriptional targets of c-FOS that repress IFN genes not defined","Single-lab pathway dissection"]},{"year":2019,"claim":"Dissecting BST2 ectodomain subregions revealed that the coiled-coil provides the ILT7-binding surface and its conformational plasticity triggers signaling while the N-terminal region suppresses activation, establishing the structural logic of receptor engagement.","evidence":"Biophysical binding studies, BST2 domain mutagenesis, coiled-coil stability analysis, homodimer binding assessment, and two orthogonal ILT7 activation assays","pmids":["31118237"],"confidence":"High","gaps":["No co-crystal or high-resolution structure of the BST2–ILT7 interface","Post-binding conformational mechanism not visualized at atomic resolution"]},{"year":2024,"claim":"Confirming Bst2-ILT7 interactions in a viral myocarditis model extended the axis beyond pDC homeostasis and HIV into tissue inflammation and therapeutic manipulation.","evidence":"Single-cell RNA sequencing of cardiac CD45+ cells, in vivo immunoglobin treatment, and coxsackievirus B3 mouse fulminant myocarditis model with ligand-receptor analysis","pmids":["39442535"],"confidence":"Low","gaps":["Mechanistic detail limited; based largely on inferred ligand-receptor interactions","Single model, single lab, causality not directly tested"]},{"year":null,"claim":"How ILT7 signaling intersects with pDC differentiation decisions and whether the BST2-ILT7 axis can be therapeutically tuned in human disease remain open.","evidence":"","pmids":[],"confidence":"Low","gaps":["No atomic-resolution structure of the BST2–ILT7 complex","Transcriptional output linking ERK-c-FOS to IFN gene repression undefined","In vivo therapeutic relevance in humans untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[0,1,10]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,1,9]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,2]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[0,1,9]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,7,9]}],"complexes":["ILT7-FcεRIγ receptor complex"],"partners":["FCER1G","BST2","SYK"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P59901","full_name":"Leukocyte immunoglobulin-like receptor subfamily A member 4","aliases":["CD85 antigen-like family member G","Immunoglobulin-like transcript 7","ILT-7"],"length_aa":499,"mass_kda":55.2,"function":"Functions coreceptor to limit the innate immune responses to viral infections; signaling occurs via FCER1G (PubMed:16735691, PubMed:19564354). Down-regulates the production of IFNA1, IFNA2, IFNA4, IFNB1 and TNF by plasmacytoid dendritic cells that have been exposed to influenza virus or cytidine-phosphate-guanosine (CpG) dinucleotides, indicating it functions as a negative regulator of TLR7 and TLR9 signaling cascades (PubMed:16735691, PubMed:19564354, PubMed:24586760). Down-regulates interferon production in response to interaction with BST2 on HIV-1 infected cells (PubMed:26172439). Activates a signaling cascade in complex with FCER1G that results in phosphorylation of Src family and Syk kinases and thereby triggers mobilization of intracellular Ca(2+) (PubMed:16735691, PubMed:19564354). Does not interfere with the differentiation of plasmacytoid dendritic cells into antigen-presenting cells (PubMed:24586760)","subcellular_location":"Cell membrane","url":"https://www.uniprot.org/uniprotkb/P59901/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/LILRA4","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/LILRA4","total_profiled":1310},"omim":[{"mim_id":"607517","title":"LEUKOCYTE IMMUNOGLOBULIN-LIKE RECEPTOR, SUBFAMILY A, MEMBER 4; LILRA4","url":"https://www.omim.org/entry/607517"},{"mim_id":"604821","title":"LEUKOCYTE IMMUNOGLOBULIN-LIKE RECEPTOR, SUBFAMILY B, MEMBER 4; LILRB4","url":"https://www.omim.org/entry/604821"},{"mim_id":"604811","title":"LEUKOCYTE IMMUNOGLOBULIN-LIKE RECEPTOR, SUBFAMILY B, MEMBER 1; LILRB1","url":"https://www.omim.org/entry/604811"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"brain","ntpm":4.3},{"tissue":"lymphoid tissue","ntpm":10.1}],"url":"https://www.proteinatlas.org/search/LILRA4"},"hgnc":{"alias_symbol":["ILT7","CD85g"],"prev_symbol":[]},"alphafold":{"accession":"P59901","domains":[{"cath_id":"2.60.40.10","chopping":"31-118","consensus_level":"high","plddt":90.7351,"start":31,"end":118},{"cath_id":"2.60.40.10","chopping":"122-218","consensus_level":"high","plddt":89.1836,"start":122,"end":218},{"cath_id":"2.60.40.10","chopping":"221-318","consensus_level":"high","plddt":90.8978,"start":221,"end":318},{"cath_id":"2.60.40.10","chopping":"322-419","consensus_level":"high","plddt":94.47,"start":322,"end":419}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P59901","model_url":"https://alphafold.ebi.ac.uk/files/AF-P59901-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P59901-F1-predicted_aligned_error_v6.png","plddt_mean":83.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=LILRA4","jax_strain_url":"https://www.jax.org/strain/search?query=LILRA4"},"sequence":{"accession":"P59901","fasta_url":"https://rest.uniprot.org/uniprotkb/P59901.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P59901/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P59901"}},"corpus_meta":[{"pmid":"19564354","id":"PMC_19564354","title":"Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction.","date":"2009","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/19564354","citation_count":258,"is_preprint":false},{"pmid":"16735691","id":"PMC_16735691","title":"Plasmacytoid dendritic cell-specific receptor ILT7-Fc epsilonRI gamma inhibits Toll-like receptor-induced interferon production.","date":"2006","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/16735691","citation_count":215,"is_preprint":false},{"pmid":"12384430","id":"PMC_12384430","title":"Subtractive hybridization reveals the expression of immunoglobulin-like transcript 7, Eph-B1, granzyme B, and 3 novel transcripts in human plasmacytoid dendritic cells.","date":"2002","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/12384430","citation_count":194,"is_preprint":false},{"pmid":"19388928","id":"PMC_19388928","title":"Extended diagnostic criteria for 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on human plasmacytoid dendritic cells. Cross-linking of ILT7 results in phosphorylation of Src family kinases and Syk kinase and induces calcium influx, blocked by Src family and Syk kinase inhibitors, indicating ITAM-mediated signaling. ILT7 cross-linking on CpG- or influenza virus-stimulated pDCs inhibits transcription and secretion of type I interferon and other cytokines.\",\n      \"method\": \"Co-immunoprecipitation of ILT7-FcεRIγ complex; anti-ILT7 cross-linking assay with kinase inhibitors; calcium flux measurement; cytokine ELISA from primary pDCs\",\n      \"journal\": \"The Journal of experimental medicine\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal functional assays with multiple orthogonal methods (co-IP, kinase phosphorylation, calcium flux, cytokine secretion) in primary pDCs, replicated across subsequent studies\",\n      \"pmids\": [\"16735691\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"BST2 (CD317) is a direct ligand of ILT7 (LILRA4). BST2 directly binds purified ILT7 protein, initiates signaling via the ILT7-FcεRIγ complex, and strongly inhibits production of type I IFN and proinflammatory cytokines by pDCs. BST2, readily induced by IFN and proinflammatory cytokines, modulates pDC IFN responses through ILT7 in a negative feedback manner.\",\n      \"method\": \"Ligand identification via ILT7-reporter cell screen; direct binding assay with purified ILT7 protein and BST2; cytokine inhibition assay with primary pDCs\",\n      \"journal\": \"The Journal of experimental medicine\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — direct binding with purified proteins, functional reporter assay, and cytokine readout in primary cells; independently replicated across multiple subsequent studies\",\n      \"pmids\": [\"19564354\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"ILT7 surface expression on pDCs requires association with the FcεRIγ adaptor molecule. ILT7 is down-regulated when pDCs mature in response to viral or bacterial stimulation. Distinct anti-ILT7 monoclonal antibodies have opposing effects: one suppresses type I IFN production in response to CpG while another up-regulates it.\",\n      \"method\": \"SAGE library screening; surface expression analysis; functional antibody cross-linking assays with CpG stimulation\",\n      \"journal\": \"International immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — SAGE expression profiling plus functional antibody cross-linking assays in primary pDCs, single lab\",\n      \"pmids\": [\"18048391\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"ILT7 (LILRA4) couples with FcεRIγ signaling adapter to activate a prominent ITAM-mediated signaling pathway in pDCs. ILT7 protein directly binds BST2 protein expressed on IFN-pre-exposed cells or cancer cell surfaces, and this interaction negatively regulates pDC TLR7/9-mediated IFN responses during viral infection.\",\n      \"method\": \"Review integrating direct binding studies and functional signaling assays from primary experiments described in source papers\",\n      \"journal\": \"Immunological reviews\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — review synthesizing prior direct binding and functional assays; no new primary data but consolidates established findings\",\n      \"pmids\": [\"20193018\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"ILT7 cross-linking suppresses pDC type I IFN production in PBMCs treated with TLR7/9 ligands or HIV, but BST2 blockade does not affect IFN-I responses even when BST2 upregulation is further boosted. ILT7 expression decreases spontaneously in pDCs upon in vitro culture correlating with pDC differentiation. BST2-mediated ILT7 cross-linking may act as a homeostatic regulatory mechanism on immature circulating pDCs rather than a negative feedback for activated mature pDCs.\",\n      \"method\": \"ILT7 cross-linking antibody treatment of PBMCs; BST2 blocking antibody; flow cytometry; cytokine measurement; HIV stimulation assay\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional cross-linking and blocking assays in primary human PBMCs, single lab, multiple conditions tested\",\n      \"pmids\": [\"23401591\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"ILT7 cross-linking on TLR7/9-stimulated pDCs mitigates upregulation of CCR7 and enhances upregulation of β7 integrin, partially reduces CD40 expression but further enhances CD86. pDCs stimulated with TLR9 ligand in the presence of ILT7 cross-linking retain ability to induce T cell proliferation and activation, suggesting ILT7 cross-linking favors differentiation of immature pDCs into antigen-presenting cells rather than IFN-producing cells.\",\n      \"method\": \"ILT7 cross-linking in PBMC cultures; flow cytometry for surface markers (CCR7, β7, CD40, CD80, CD86); pDC-T cell co-culture with SEB stimulation; T cell proliferation assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional cross-linking assays with multiple surface marker readouts and T cell co-culture functional readout, single lab\",\n      \"pmids\": [\"24586760\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"HIV-1 Vpu suppresses TLR7-mediated IFN-I production by pDCs through a mechanism relying on BST2-ILT7 interaction. While Vpu downregulates surface BST2 to counteract viral restriction, it also re-locates remaining BST2 molecules outside viral assembly sites where they remain free to bind and activate ILT7 upon cell-to-cell contact, thereby suppressing pDC antiviral responses.\",\n      \"method\": \"Cell-to-cell contact assay between HIV-producing T cells and pDCs; Vpu mutant constructs; IFN-I production measurement; BST2 surface localization imaging; ILT7 cross-linking functional assay\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (mutant constructs, cell contact assays, localization imaging, functional cytokine readout) establishing mechanism, single rigorous lab study\",\n      \"pmids\": [\"26172439\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Syk kinase plays a dual role in pDC signaling: it positively regulates TLR7/9-mediated IFN-α production and also mediates inhibitory regulatory receptor (ILT7 and BDCA-2) signaling that suppresses TLR-induced IFN production. A Syk inhibitor at concentrations insufficient to block TLR7/9 signaling still released the IFN-α block triggered via ILT7 pathway, partially restoring pDC IFN production.\",\n      \"method\": \"Pharmacological Syk inhibition (AB8779) in primary pDCs and GEN2.2 cell line; TLR7/9 agonist stimulation; ILT7 cross-linking; IFN-α/cytokine measurement; phosphorylation kinetics analysis (Y352, Y525/526)\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — pharmacological targeting with specific inhibitor, differential phosphorylation kinetics, multiple cell systems tested, single lab\",\n      \"pmids\": [\"27258042\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"HIV-1 group O Nef, unlike HIV-1 group M Vpu, does not efficiently displace short BST2 from viral assembly sites and consequently impairs BST2 ability to activate ILT7 signaling to suppress pDC IFN-I responses during sensing of infected cells.\",\n      \"method\": \"Comparison of O-Nef vs M-Vpu BST2 counteraction; cell-to-cell sensing assay with pDC-containing PBMCs; IFN-I measurement; BST2 surface localization analysis\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — comparative viral protein functional assay with pDC IFN readout and localization analysis, single lab\",\n      \"pmids\": [\"27581991\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"ILT7 (BDCA-2 and ILT7) cross-linking activates a BCR-like signaling pathway that inhibits TLR9-mediated type I IFN production through the MEK1/2-ERK-c-FOS signaling axis in pDCs. MEK1/2 inhibitors potentiated TLR9-mediated IFN-I production and partially restored IFN-α production blocked by ILT7 engagement, correlating with abrogation of MEK1/2-ERK-c-FOS signaling.\",\n      \"method\": \"ILT7/BDCA-2 mAb cross-linking; BST2-expressing cell stimulation; MEK1/2 inhibitors (PD0325901, U0126); c-FOS expression and phosphorylation analysis; IFN-I cytokine measurement in GEN2.2 cells and primary pDCs\",\n      \"journal\": \"Frontiers in immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — pharmacological and genetic pathway dissection with multiple inhibitors and downstream marker readouts in two cell systems, single lab\",\n      \"pmids\": [\"29535732\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Structurally distinct regions of the BST2 ectodomain govern ILT7 activation differently: the coiled-coil region contains a newly defined ILT7-binding surface, while the N-terminal region suppresses ILT7 activation. A stable BST2 homodimer binds to ILT7, but post-binding events associated with BST2 coiled-coil plasticity are required to trigger receptor signaling. BST2 with unstable or rigid coiled-coil fails to activate ILT7, whereas N-terminal region substitutions enhance activation.\",\n      \"method\": \"Biophysical binding studies; two functional ILT7 activation assays; BST2 domain mutagenesis; coiled-coil stability analysis; homodimer binding assessment\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — mutagenesis combined with biophysical binding studies and two orthogonal functional activation assays defining structural mechanism; rigorous single-paper study\",\n      \"pmids\": [\"31118237\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"ILT7 ligand (identified as BST2) is expressed on all tested human cancer cell lines and on noncancerous cells exposed to IFN-α, IFN-β, IFN-γ, TNF-α, IL-1β, TGF-β, LPS, or imiquimod. High ILT7L-expressing cancer cells inhibit IFN-α and TNF-α production by CpG-stimulated pDCs. NF-κB and mTOR signaling pathways are involved in regulating ILT7L expression on cancer cells.\",\n      \"method\": \"ILT7-GFP reporter cell system to detect ILT7 ligand; cytokine stimulation assays; pharmacological inhibition of NF-κB and mTOR; IFN-α/TNF-α measurement by ELISA\",\n      \"journal\": \"Clinical cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional reporter assay system plus pharmacological pathway analysis, single lab, multiple orthogonal readouts\",\n      \"pmids\": [\"19723650\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"ILT7 transcript is selectively expressed in human plasmacytoid dendritic cells compared to monocyte-derived dendritic cells, identified by cDNA subtractive hybridization.\",\n      \"method\": \"cDNA subtractive hybridization comparing pDCs vs monocyte-derived DCs\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — discovery of pDC-selective expression by subtractive hybridization, replicated in subsequent studies\",\n      \"pmids\": [\"12384430\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"BST2-ILT7 ligand-receptor-mediated cellular interactions are manipulated by immunoglobin treatment in fulminant myocarditis, with Bst2-ILT7 interactions confirmed in vivo in a coxsackievirus B3 mouse model.\",\n      \"method\": \"Single-cell RNA sequencing of cardiac CD45+ cells; in vivo immunoglobin treatment; coxsackievirus B3 mouse FM model; ligand-receptor interaction analysis\",\n      \"journal\": \"British journal of pharmacology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — ligand-receptor interaction confirmed in vivo but mechanistic detail is limited in the abstract; single lab, single model\",\n      \"pmids\": [\"39442535\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"LILRA4 (ILT7) is a plasmacytoid dendritic cell-specific activating receptor that forms a complex with the FcεRIγ signaling adapter; upon engagement by its ligand BST2 (CD317), ILT7 triggers ITAM-mediated phosphorylation of Src family kinases and Syk, inducing calcium influx and downstream MEK1/2-ERK-c-FOS signaling, which collectively inhibits TLR7/9-induced type I interferon and proinflammatory cytokine production by pDCs; BST2 engages ILT7 through its coiled-coil ectodomain as a stable homodimer requiring coiled-coil conformational plasticity for receptor activation, while the BST2 N-terminal region suppresses activation, establishing a structural negative-feedback mechanism that limits pDC IFN responses after viral infection or IFN exposure.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"LILRA4 (ILT7) is a plasmacytoid dendritic cell (pDC)-selective activating receptor that acts as a negative regulator of type I interferon responses [#0, #12]. It lacks intrinsic signaling motifs and instead pairs with the ITAM-bearing adaptor FcεRIγ, an association required for its surface expression; cross-linking of the ILT7–FcεRIγ complex drives phosphorylation of Src-family kinases and Syk, calcium influx, and downstream MEK1/2–ERK–c-FOS signaling that suppresses TLR7/9-induced type I IFN and proinflammatory cytokine production [#0, #2, #9]. Syk occupies a pivotal node, since it both promotes TLR-driven IFN-α and transmits the inhibitory ILT7 signal [#7]. The physiological ligand is BST2 (CD317), which binds purified ILT7 directly and engages it as a stable homodimer through a coiled-coil ectodomain surface, with coiled-coil conformational plasticity required for receptor triggering and the BST2 N-terminal region acting to suppress activation—establishing a structural negative-feedback loop in which IFN- and cytokine-induced BST2 restrains pDC IFN output [#1, #10, #11]. This axis is exploited during HIV-1 infection: HIV-1 Vpu relocates BST2 away from viral assembly sites so it remains free to engage and activate ILT7 during cell-to-cell contact, dampening pDC antiviral IFN, a function not efficiently performed by HIV-1 group O Nef [#6, #8].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Establishing that ILT7 is a pDC-restricted gene defined the cell type in which its receptor function would later be interpreted.\",\n      \"evidence\": \"cDNA subtractive hybridization comparing pDCs to monocyte-derived DCs\",\n      \"pmids\": [\"12384430\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Expression pattern alone did not address receptor function\", \"No ligand or signaling partner identified at this stage\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"The discovery that ILT7 partners with FcεRIγ and triggers Src/Syk-dependent calcium flux to suppress IFN answered how a receptor with no signaling motif regulates pDCs.\",\n      \"evidence\": \"Co-IP of the ILT7–FcεRIγ complex, anti-ILT7 cross-linking with kinase inhibitors, calcium flux, and cytokine ELISA in primary pDCs\",\n      \"pmids\": [\"16735691\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"The natural ligand was not yet identified\", \"Downstream effectors beyond proximal Src/Syk kinases unresolved\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Showing that FcεRIγ association is required for ILT7 surface expression and that distinct antibodies have opposing effects clarified the receptor's assembly and dynamic regulation.\",\n      \"evidence\": \"SAGE screening, surface expression analysis, and functional antibody cross-linking with CpG stimulation in primary pDCs\",\n      \"pmids\": [\"18048391\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis for opposing antibody effects not defined\", \"Single-lab functional data\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Identifying BST2 as the direct ligand defined a negative-feedback circuit, since BST2 is induced by IFN and cytokines and then activates ILT7 to shut down pDC IFN.\",\n      \"evidence\": \"ILT7-reporter ligand screen, direct binding with purified ILT7 and BST2, and cytokine inhibition in primary pDCs; complemented by reporter-based detection of BST2 on cancer cells and IFN/cytokine-exposed cells\",\n      \"pmids\": [\"19564354\", \"19723650\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of BST2–ILT7 binding not yet defined\", \"Whether feedback operates on immature versus mature pDCs unresolved\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Testing BST2 blockade and culture-induced ILT7 loss reframed the BST2-ILT7 axis as a homeostatic control on immature circulating pDCs rather than a feedback brake on activated pDCs.\",\n      \"evidence\": \"ILT7 cross-linking and BST2 blocking antibodies in primary human PBMCs with TLR7/9 ligands and HIV stimulation, flow cytometry, cytokine measurement\",\n      \"pmids\": [\"23401591\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"BST2 blockade failing to alter IFN-I leaves the in vivo dominance of the axis unclear\", \"Single-lab observation\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Demonstrating that ILT7 engagement reshapes pDC surface markers and preserves T-cell stimulatory capacity established that the receptor biases differentiation toward antigen presentation rather than IFN production.\",\n      \"evidence\": \"ILT7 cross-linking in PBMC cultures with surface-marker flow cytometry and pDC–T cell co-culture proliferation assays\",\n      \"pmids\": [\"24586760\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Signaling link between ILT7 and the differentiation phenotype not mapped\", \"In vivo relevance untested\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Showing that HIV-1 Vpu relocates BST2 to keep it free to activate ILT7 explained how the virus co-opts this inhibitory axis to suppress pDC antiviral IFN.\",\n      \"evidence\": \"Cell-to-cell contact assays between HIV-producing T cells and pDCs, Vpu mutants, BST2 surface localization imaging, and ILT7 cross-linking functional readout\",\n      \"pmids\": [\"26172439\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Quantitative contribution of this axis to overall HIV immune evasion not established\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Defining Syk's dual role and the MEK1/2-ERK-c-FOS axis, together with comparative viral protein analysis, resolved the downstream signaling cascade and showed it is differentially exploited across HIV lineages.\",\n      \"evidence\": \"Pharmacological Syk inhibition and phosphorylation kinetics in pDCs and GEN2.2 cells; comparative O-Nef versus M-Vpu BST2-relocation and pDC IFN sensing assays\",\n      \"pmids\": [\"27258042\", \"27581991\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How Syk discriminates activating TLR versus inhibitory ILT7 signals not resolved\", \"Single-lab pharmacological dissection\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Mapping the inhibitory pathway to a BCR-like MEK1/2-ERK-c-FOS cascade identified the specific effector module through which ILT7 suppresses TLR9-driven IFN.\",\n      \"evidence\": \"ILT7/BDCA-2 cross-linking with MEK1/2 inhibitors, c-FOS expression/phosphorylation, and IFN-I measurement in GEN2.2 cells and primary pDCs\",\n      \"pmids\": [\"29535732\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Transcriptional targets of c-FOS that repress IFN genes not defined\", \"Single-lab pathway dissection\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Dissecting BST2 ectodomain subregions revealed that the coiled-coil provides the ILT7-binding surface and its conformational plasticity triggers signaling while the N-terminal region suppresses activation, establishing the structural logic of receptor engagement.\",\n      \"evidence\": \"Biophysical binding studies, BST2 domain mutagenesis, coiled-coil stability analysis, homodimer binding assessment, and two orthogonal ILT7 activation assays\",\n      \"pmids\": [\"31118237\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No co-crystal or high-resolution structure of the BST2–ILT7 interface\", \"Post-binding conformational mechanism not visualized at atomic resolution\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Confirming Bst2-ILT7 interactions in a viral myocarditis model extended the axis beyond pDC homeostasis and HIV into tissue inflammation and therapeutic manipulation.\",\n      \"evidence\": \"Single-cell RNA sequencing of cardiac CD45+ cells, in vivo immunoglobin treatment, and coxsackievirus B3 mouse fulminant myocarditis model with ligand-receptor analysis\",\n      \"pmids\": [\"39442535\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Mechanistic detail limited; based largely on inferred ligand-receptor interactions\", \"Single model, single lab, causality not directly tested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How ILT7 signaling intersects with pDC differentiation decisions and whether the BST2-ILT7 axis can be therapeutically tuned in human disease remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No atomic-resolution structure of the BST2–ILT7 complex\", \"Transcriptional output linking ERK-c-FOS to IFN gene repression undefined\", \"In vivo therapeutic relevance in humans untested\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [0, 1, 10]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1, 9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [0, 1, 9]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 7, 9]}\n    ],\n    \"complexes\": [\"ILT7-FcεRIγ receptor complex\"],\n    \"partners\": [\"FCER1G\", \"BST2\", \"SYK\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}