Affinage

TLR3

Toll-like receptor 3 · UniProt O15455

Round 2 corrected
Length
904 aa
Mass
103.8 kDa
Annotated
2026-04-28
130 papers in source corpus 49 papers cited in narrative 49 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TLR3 is an innate immune pattern-recognition receptor that senses double-stranded RNA—of viral, endogenous, or damage-associated origin—within endosomes and at the cell surface, transducing signals that activate type I interferon production, NF-κB-dependent inflammatory gene expression, and regulated cell death programs. Structurally, TLR3 forms a horseshoe-shaped leucine-rich repeat solenoid that dimerizes upon dsRNA binding (minimum ~21–45 bp) and cooperatively clusters along longer dsRNA at 103 Å inter-dimer spacing, with this higher-order assembly driving efficient signaling (PMID:15961631, PMID:36371424, PMID:36631495). Signaling proceeds predominantly through the adaptor TRIF (recruited with the aid of WDFY1 and ZCCHC3), which bifurcates into IKKε/TBK1-mediated IRF3 activation for IFN-β induction, RIP1-dependent NF-κB activation, and FADD/caspase-8-dependent apoptosis or RIPK3/MLKL-dependent necroptosis including Ripoptosome and NLRP3 inflammasome engagement; a TRIF-independent branch recruits c-Src to regulate cell migration (PMID:12855817, PMID:15064760, PMID:21737330, PMID:26104484, PMID:22323545). Dominant-negative TLR3 mutations cause herpes simplex encephalitis in otherwise healthy children by abolishing cell-intrinsic CNS antiviral defense, and TLR3 additionally maintains constitutive basal IFN-β in fibroblasts and neurons, drives IL-6/STAT3-dependent wound-induced hair follicle neogenesis, and shapes pre-metastatic niches via endothelial chemokine and SLIT2 induction (PMID:17872438, PMID:33393505, PMID:26253200, PMID:32999457).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2001 High

    Identification of TLR3 as the innate receptor for dsRNA resolved how the mammalian immune system detects viral replication intermediates, establishing the foundation for all subsequent TLR3 mechanistic work.

    Evidence TLR3 knockout mice challenged with poly(I:C), measuring NF-κB activation and cytokine responses

    PMID:11607032

    Open questions at the time
    • Adaptor mechanism unknown at this point
    • Whether TLR3 has endogenous ligands not yet addressed
    • Structural basis of dsRNA recognition unresolved
  2. 2002 High

    Discovery of the TRIF/TICAM-1 adaptor and the TLR3-IRF3 axis explained how TLR3 produces type I interferons independently of MyD88, establishing the MyD88-independent signaling branch as the defining feature of TLR3.

    Evidence Co-immunoprecipitation of TRIF with TLR3 TIR domain, dominant-negative TRIF, IRF3 loss-of-function, IFN-β reporter assays

    PMID:12354379 PMID:12471095 PMID:12539043

    Open questions at the time
    • Kinases phosphorylating IRF3 downstream of TRIF not yet identified
    • TRIF essentiality not confirmed by genetic knockout at this point
  3. 2003 High

    Genetic confirmation that TRIF is essential and identification of IKKε/TBK1 as the kinases activating IRF3 completed the core signaling cascade from TLR3 to IFN-β.

    Evidence TRIF-deficient mice with abolished TLR3-mediated IFN-β; kinase assays and dominant-negative constructs identifying IKKε and TBK1

    PMID:12692549 PMID:12855817

    Open questions at the time
    • NF-κB branch mediator downstream of TRIF not yet identified
    • Structural basis of TLR3 recognition still unresolved
  4. 2004 High

    Identification of RIP1 as the NF-κB mediator downstream of TRIF and recognition that endogenous RNA from necrotic cells acts as a TLR3 DAMP extended TLR3 biology beyond viral defense to sterile inflammation.

    Evidence RIP1 KO cells showing abolished NF-κB but intact IFN-β; necrotic cell RNA activating TLR3 reporters and DC maturation

    PMID:14729660 PMID:15064760

    Open questions at the time
    • Structural mechanism of dsRNA binding unresolved
    • In vivo DAMP relevance not yet demonstrated
  5. 2005 High

    The 2.1 Å crystal structure of TLR3's ectodomain revealed the horseshoe solenoid architecture and glycosylation-free dsRNA-binding face, while discovery that nucleoside modifications suppress TLR3 activation explained discrimination of self versus foreign RNA.

    Evidence X-ray crystallography at 2.1 Å; modified RNA stimulation of TLR3 reporter cells

    PMID:15961631 PMID:16111635

    Open questions at the time
    • No structure of the TLR3-dsRNA complex yet
    • Minimum dsRNA length for activation unclear
    • Transmembrane and intracellular domain arrangement unknown
  6. 2007 High

    The discovery that dominant-negative TLR3 mutations cause herpes simplex encephalitis in children established TLR3 as non-redundant for CNS antiviral defense in humans, linking the receptor to a defined Mendelian disease.

    Evidence Patient genetic analysis with functional validation in patient fibroblasts and HSV-1 susceptibility testing

    PMID:17872438

    Open questions at the time
    • Why TLR3 is specifically required in the CNS but not periphery not fully explained
    • Cell-intrinsic versus immune cell contribution not separated
  7. 2008 High

    Demonstration that siRNAs ≥21 nt activate cell-surface TLR3 to suppress neovascularization established a minimum length threshold and revealed TLR3 operates at the plasma membrane, not only in endosomes; concomitant identification of SIRPα as a negative regulator defined the first inhibitory checkpoint on TLR3 signaling.

    Evidence TLR3-/- and TRIF-/- mice in CNV models with length-dependent siRNA controls; SIRPα knockdown with PI3K/IRF3 pathway analysis

    PMID:18368052 PMID:18471880 PMID:19359485

    Open questions at the time
    • Structural basis for minimum length requirement unknown
    • SIRPα regulation only demonstrated by single lab
  8. 2011 High

    Biochemical purification of the Ripoptosome—a 2 MDa complex of RIP1/FADD/caspase-8/cFLIP—as a TLR3-inducible platform resolved how TLR3-TRIF signaling bifurcates between apoptosis and RIP3-dependent necroptosis.

    Evidence Size exclusion chromatography, Co-IP, caspase activity assays with necroptosis inhibitors

    PMID:21737330

    Open questions at the time
    • Upstream trigger for Ripoptosome assembly versus NF-κB signaling not fully delineated
    • Role of cIAP depletion in physiological settings unclear
  9. 2012 High

    Identification of UVB-damaged self-RNA as an endogenous TLR3 ligand in skin and a TRIF-independent c-Src signaling branch for migration extended TLR3 function beyond canonical innate immunity into tissue damage sensing and cell motility.

    Evidence TLR3-/- mice after UVB exposure; TRIF-/- and MyD88-/- cell migration assays with Src Co-IP and lipid raft fractionation

    PMID:22323545 PMID:22772463

    Open questions at the time
    • Precise molecular mechanism of c-Src recruitment to TLR3 undefined
    • Whether UVB-damaged RNA generates a specific dsRNA structure unclear
  10. 2014 High

    Multiple in vivo studies established TLR3 as a pathological mediator in sterile tissue injury—myocardial ischemia-reperfusion and radiation-induced gastrointestinal syndrome—and revealed S100A9-dependent endosomal trafficking as a gating step for TLR3 ligand encounter.

    Evidence TLR3-/- mice in cardiac I/R and radiation models; S100A9 KO macrophages with endosomal fractionation and confocal co-localization

    PMID:24390148 PMID:24637670 PMID:26385519

    Open questions at the time
    • Whether S100A9-dependent trafficking is universal across cell types unknown
    • Therapeutic window for TLR3 inhibition in sterile injury not defined
  11. 2015 High

    Elucidation of the TLR3-TRIF-RIPK1/RIPK3/MLKL-NLRP3 inflammasome axis and identification of WDFY1 as a TRIF recruitment adaptor refined the signaling architecture, while TLR3-IL-6/STAT3-driven hair follicle neogenesis revealed a regenerative function; TRIM8-mediated K6/K33-linked polyubiquitination of TRIF defined a shutdown mechanism.

    Evidence Caspase-8 catalytic mutants and RIPK1/3/MLKL KO macrophages for inflammasome; WDFY1 Co-IP/KD; TLR3-/- wound-induced hair neogenesis model; TRIM8 KO mice with ubiquitination assays

    PMID:25736436 PMID:26104484 PMID:26253200 PMID:28747347

    Open questions at the time
    • WDFY1 and TRIM8 findings each from single labs
    • Relative contribution of individual negative regulators in vivo unclear
  12. 2016 High

    LUBAC was identified as a pro-survival component of the TLR3 signaling complex whose absence converts TLR3 signaling from gene activation to death, explaining cpdm dermatitis; concurrently, tumor exosomal snRNAs were identified as TLR3 ligands that build pre-metastatic lung niches.

    Evidence LUBAC component KO mice with cpdm/Tlr3 double-KO rescue; TLR3-/- mice in metastasis models with exosome RNA fractionation

    PMID:27505671 PMID:27810922

    Open questions at the time
    • Which RNA species in exosomes are the primary TLR3 agonists not fully defined
    • LUBAC's precise site of action within the TLR3 complex not structurally resolved
  13. 2018 High

    Discovery that TLR3 recruits mTORC2 and that mTORC2-dependent peripheral trafficking enables mTORC1 activation for IFN induction in neurons linked TLR3 to metabolic kinase signaling, providing a mechanistic basis for its non-redundant CNS antiviral role.

    Evidence Co-IP of TLR3-mTORC2, TLR3 trafficking imaging, mTOR inhibitor plus agonistic anti-TLR3 antibody rescue in HSV-1 intracranial model

    PMID:30201994

    Open questions at the time
    • Whether mTORC2 recruitment occurs in non-neuronal cells unknown
    • Structural interface between TLR3 and mTORC2 undefined
  14. 2019 Medium

    Identification of ZCCHC3 and ZFYVE1 as positive regulators—one promoting TRIF recruitment, the other enhancing ligand binding affinity—revealed that TLR3 activation is controlled by a multi-accessory protein assembly rather than simple receptor-ligand interaction.

    Evidence ZCCHC3 and ZFYVE1 KO mice with Co-IP, poly(I:C) binding assays, cytokine measurements

    PMID:31388100 PMID:32133501

    Open questions at the time
    • Both studies from single labs
    • Whether ZCCHC3 and ZFYVE1 act sequentially or simultaneously unclear
    • Structural basis of accessory protein assembly unknown
  15. 2021 High

    Demonstration that TLR3 maintains constitutive basal IFN-β in fibroblasts and cortical neurons, independent of exogenous dsRNA stimulation, reframed TLR3 as a tonic signaling receptor essential for steady-state antiviral readiness.

    Evidence TLR3-deficient human fibroblasts and iPSC-derived cortical neurons with basal IFN-β ELISA and ISG qRT-PCR; multi-virus susceptibility panel

    PMID:33393505

    Open questions at the time
    • Endogenous ligand driving constitutive signaling not identified
    • Whether basal signaling uses the same TRIF-dependent pathway as stimulated signaling not fully resolved
  16. 2022 High

    Cryo-EM structures of full-length TLR3 on long dsRNA revealed cooperative dimer clustering at uniform 103 Å spacing, finally explaining the long-known dsRNA length-dependence of TLR3 activation at an atomic level; concurrently, ZBP1 was shown to facilitate RIPK1 delivery to TRIF and PKR was found to synergize with TLR3 for apoptosis by depleting cFLIP.

    Evidence Cryo-EM of full-length TLR3 + ~400 bp dsRNA with deletion mutants; ZBP1 KO mice with RIPK1 ubiquitination assays; PKR/TLR3 double KO cells with caspase-8 and cFLIP analysis

    PMID:35666872 PMID:35970851 PMID:36371424 PMID:36631495

    Open questions at the time
    • No structure of the intracellular TRIF-recruited signalosome yet
    • Cooperative clustering threshold for signaling versus non-signaling states not quantitatively defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The endogenous ligand(s) responsible for TLR3's constitutive basal IFN-β signaling remain unidentified, no structure of the full intracellular TLR3-TRIF signalosome exists, and the mechanistic basis for cell-type-specific outcomes (e.g., CNS-specific requirement, regenerative vs. pathological roles) is not resolved.
  • Identity of constitutive endogenous TLR3 ligand unknown
  • No atomic structure of the TRIF-containing intracellular signaling platform
  • How cell-type context determines pro-inflammatory vs. regenerative vs. death outcomes not mechanistically explained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 6 GO:0140299 molecular sensor activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005768 endosome 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 10 R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 4 R-HSA-5357801 Programmed Cell Death 4
Partners
IKBKERIPK1S100A9TBK1TICAM1WDFY1ZCCHC3ZFYVE1
Complex memberships
RipoptosomeTLR3 homodimer

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 TLR3 recognizes double-stranded RNA (dsRNA) and activates NF-κB and type I interferon production; TLR3-deficient mice showed reduced responses to poly(I:C) and resistance to its lethal effects, establishing TLR3 as the dsRNA pattern-recognition receptor of the innate immune system. TLR3 knockout mice, poly(I:C) challenge, NF-κB reporter assays, cytokine measurement Nature High 11607032
2002 TLR3 activates IRF3 to induce a specific antiviral gene program including IFN-β; this TLR3/TLR4-IRF3 pathway is distinct from other TLRs and potently inhibits viral replication. Gene expression profiling, IRF3 loss-of-function analysis, viral replication assays Immunity High 12354379
2002 TRIF (TIR domain-containing adaptor inducing IFN-β) is a novel adaptor that physically associates with TLR3's TIR domain and activates both the NF-κB-dependent and IFN-β promoters; dominant-negative TRIF inhibits TLR3-dependent signaling. Co-immunoprecipitation, dominant-negative overexpression, reporter assays Journal of immunology High 12471095
2003 TRIF-deficient mice are defective in both TLR3- and TLR4-mediated IFN-β expression and IRF-3 activation, demonstrating that TRIF is the essential adaptor for the MyD88-independent TLR3 signaling pathway. Gene knockout mice, cytokine ELISA, IRF-3 activation assays Science High 12855817
2003 TICAM-1 (also called TRIF) physically binds the TIR domain of TLR3 and mediates dsRNA-TLR3-dependent IFN-β production independently of MyD88 and TIRAP. Co-immunoprecipitation, IFN-β promoter reporter assay, poly(I:C) stimulation Nature immunology High 12539043
2003 IKKε and TBK1 are essential kinase components of the IRF3 signaling pathway downstream of TLR3; TLR3 stimulation by dsRNA coordinates activation of both IRF3 and NF-κB through these kinases. Kinase assays, dominant-negative constructs, reporter assays, co-immunoprecipitation Nature immunology High 12692549
2004 RIP1 kinase is recruited by TRIF via its RIP homotypic interaction motif and is an essential mediator of TLR3-induced NF-κB activation; RIP3 negatively regulates this pathway. In the absence of RIP1, TLR3-mediated NF-κB (but not JNK or IFN-β) signaling is abolished. RIP1 knockout cells, co-immunoprecipitation, NF-κB reporter assays Nature immunology High 15064760
2004 mRNA and RNA from necrotic cells act as endogenous TLR3 ligands; TLR3 activation by host-derived RNA induces NF-κB, IL-8, and DC maturation via tyrosine phosphorylation, establishing endogenous RNA as a DAMP activating TLR3. TLR3-expressing HEK293 reporter cells, RNase treatment, dendritic cell maturation assays, NF-κB luciferase reporter The Journal of biological chemistry High 14729660
2004 TLR3 is constitutively expressed in human alveolar and bronchial epithelial cells; it mediates the innate immune response to influenza A virus and dsRNA through TRIF (not MyD88), involving MAPK and PI3K/Akt signaling, leading to IL-8, IL-6, RANTES, IFN-β secretion and ICAM-1 upregulation. siRNA knockdown, dominant-negative constructs, cytokine ELISA, intracellular localization assays The Journal of biological chemistry High 15579900
2005 Crystal structure of the human TLR3 ectodomain at 2.1 Å reveals a large horseshoe-shaped solenoid of 23 leucine-rich repeats; one glycosylation-free face is implicated in ligand binding and oligomerization, with positively charged patches providing a dsRNA binding site. X-ray crystallography at 2.1 Å resolution Science High 15961631
2005 Nucleoside modifications (m5C, m6A, m5U, s2U, pseudouridine) incorporated into RNA suppress TLR3 (and TLR7/8) activation; mammalian RNA, which is abundant in modified nucleosides, is poorly stimulatory, while bacterial and mitochondrial RNA (lacking modifications) potently activate TLR3. TLR3-reporter HEK293 cells, in vitro transcribed modified RNAs, cytokine measurement in dendritic cells Immunity High 16111635
2005 TLR3 activation on mast cells via poly(I:C) induces TLR3 phosphorylation and upregulation of IFN-β, ISG15, IP-10, and RANTES; mast-cell TLR3 activation potently stimulates CD8+ T-cell recruitment, and mast-cell-deficient mice show decreased CD8+ T-cell influx after poly(I:C) injection. In vivo poly(I:C) injection, mast-cell-deficient mice, reconstitution experiments, flow cytometry Blood High 15840693
2006 Microglia recognize dsRNA through TLR3, leading to MAPK activation, TNF-α/IL-6 secretion, and morphological activation; TLR3-deficient microglia show impaired cytokine production and delayed MAPK kinetics; in vivo intracerebroventricular poly(I:C) causes microgliosis in WT but not TLR3-/- mice. Primary microglia cultures from TLR3-/- mice, in vivo intracerebroventricular injection, immunofluorescence Journal of immunology High 16517751
2007 A dominant-negative TLR3 allele causes impaired TLR3 signaling and susceptibility to HSV-1 encephalitis in otherwise healthy children; TLR3 is required for CNS control of HSV-1 but is redundant for defense against most other pathogens, establishing a cell-intrinsic CNS-specific role for TLR3. Patient genetic analysis, in vitro TLR3 functional assays in patient fibroblasts, HSV-1 susceptibility testing Science High 17872438
2008 siRNAs of ≥21 nucleotides suppress choroidal neovascularization via cell-surface TLR3 and its adaptor TRIF, inducing IFN-γ and IL-12; this is sequence- and target-independent, not mediated by RNAi or IFN-α/β; a minimum 21-nt length is required to bridge a modelled 2:1 TLR3-RNA complex; the TLR3 coding variant 412FF renders endothelial cells refractory to siRNA-induced cytotoxicity. Mouse CNV models, TLR3-/- mice, TRIF-/- mice, pharmacogenetic analysis, modelled TLR3-RNA complex Nature High 18368052
2008 Signal regulatory protein alpha (SIRPα) negatively regulates TLR3-dependent IRF3 and MAPK pathways; upon poly(I:C) stimulation, SIRPα recruits PI3K to its phosphorylated tyrosine residues, reducing downstream AKT activity and thereby inhibiting IFN-β induction. siRNA knockdown of SIRPα, PI3K inhibitor treatment, IRF3 activation assays, IFN-β promoter reporters Molecular immunology Medium 18471880
2009 21-nt nontargeted siRNA suppresses both hemangiogenesis and lymphangiogenesis by triggering phosphorylation of cell-surface TLR3 on lymphatic endothelial cells and inducing apoptosis; a 7-nt siRNA too short to activate TLR3 has no effect, confirming length-dependent TLR3 activation. Mouse corneal suture and hindlimb ischemia models, TLR3 phosphorylation assays, apoptosis assays PNAS High 19359485
2009 Commensal staphylococcal lipoteichoic acid (LTA) inhibits TLR3-triggered inflammation in keratinocytes via TLR2; TLR3 activation is required for normal inflammatory cytokine release (TNF-α, IL-6) from keratinocytes in response to RNA from damaged cells after skin injury. TLR3-/- mouse skin model, keratinocyte cultures, cytokine measurement, TLR2-/- comparison Nature medicine High 19966777
2011 Ripoptosome — a 2 MDa intracellular complex containing RIP1, FADD, caspase-8, caspase-10, and cFLIP isoforms — forms downstream of TLR3 activation when cIAPs are absent; cFLIP isoforms differentially regulate whether the outcome is apoptosis or RIP3-dependent necroptosis. Co-immunoprecipitation, size exclusion chromatography, caspase activity assays, necroptosis inhibitor studies Molecular cell High 21737330
2012 A TRIF-independent branch of TLR3 signaling controls cell migration, adhesion, and proliferation; upon dsRNA stimulation, TLR3 recruits the proto-oncoprotein c-Src (independent of TRIF and MyD88), leading to biphasic regulation of cell motility — initial activation followed by inhibition through Src sequestration in lipid rafts. TRIF-/- and MyD88-/- cells, live cell migration assays, Src co-immunoprecipitation, lipid raft fractionation Journal of immunology High 22323545
2012 UVB radiation damages noncoding RNA (including U1 RNA), and UVB-damaged self-RNA activates TLR3 and TRIF to induce TNF-α and IL-6 production from keratinocytes and PBMCs; TLR3-/- mice fail to upregulate TNF-α in skin after UVB exposure; TLR3 is also necessary for UVB-induced immune suppression. TLR3-/- mice, whole-transcriptome sequencing, purified noncoding RNA stimulation assays, TRIF-/- comparison Nature medicine High 22772463
2014 Extracellular RNA released during myocardial ischemia-reperfusion activates TLR3-TRIF signaling to promote cardiomyocyte apoptosis and infarction; TLR3-/- or TRIF-/- mice show smaller infarcts and better cardiac function; RNase treatment reduces serum RNA, attenuates cytokine production, and confers cardiac protection. Coronary artery occlusion model in TLR3-/-, TRIF-/-, IFNAR1-/- mice; RNase in vivo treatment; cardiomyocyte apoptosis assays Journal of the American Heart Association High 24390148
2014 TLR3 activation by poly(I:C) induces upregulation of miR-29b, -29c, -148b, and -152, which target DNA methyltransferases, leading to demethylation and reexpression of the epigenetically silenced tumor suppressor RARβ, sensitizing cancer cells to retinoic acid-induced apoptosis. miRNA profiling, DNMT target validation, RARβ promoter methylation analysis, in vitro and in vivo tumor models PNAS Medium 23716670
2014 S100A9 is required for TLR3 trafficking from early endosomes to late endosomes (the compartment competent for ligand recognition); S100A9 co-localizes and interacts with TLR3 after poly(I:C) treatment; in S100A9-KO macrophages, TLR3 fails to reach late endosomes and cannot co-localize with its ligand, abolishing downstream cytokine production. S100A9 knockout macrophages, confocal co-localization, co-immunoprecipitation, endosomal fractionation, biotin-poly(I:C) tracking Journal of immunology High 26385519
2014 TLR3 activation by dsRNA from damaged intestinal epithelium triggers lethal gastrointestinal syndrome after high-dose irradiation; cellular RNA released from p53-dependent crypt cell death induces TLR3-mediated bystander cell death; TLR3-/- mice have significantly reduced radiation-induced crypt cell death; a TLR3-RNA binding inhibitor ameliorates the syndrome. TLR3-/- mice, irradiation model, TLR3 inhibitor treatment, crypt survival assays Nature communications High 24637670
2015 TLR3 binding to dsRNA promotes NLRP3 inflammasome activation through TRIF/RIPK1/FADD-dependent intermediate and late pathways; the scaffolding (not catalytic) function of caspase-8 provides a post-translational signal 1 in the intermediate pathway, while the late pathway additionally requires kinase-competent RIPK3 and MLKL for both signals 1 and 2. Caspase-8 catalytic mutants, RIPK1/RIPK3/MLKL KO macrophages, inflammasome reconstitution assays Nature communications High 26104484
2015 dsRNA released from damaged skin activates TLR3, which signals through IL-6 and STAT3 to promote wound-induced hair follicle neogenesis; TLR3-/- animals fail to initiate this regeneration program; TLR3 activation induces hair follicle stem cell markers and morphogenetic pathways including EDAR, Wnt, and Shh. TLR3-/- mice, wound-induced hair neogenesis model, IL-6/STAT3 pathway analysis, stem cell marker expression Cell stem cell High 26253200
2015 WDFY1 is an adaptor protein that interacts with both TLR3 and TLR4 and mediates recruitment of TRIF to these receptors; WDFY1 overexpression potentiates TLR3/4-mediated NF-κB, IRF3 activation, and type I IFN production; WDFY1 depletion has the opposite effect. Co-immunoprecipitation, WDFY1 overexpression and siRNA knockdown, NF-κB/IRF3 reporter assays EMBO reports Medium 25736436
2015 TLR3 controls TRIF-dependent TLR3/4 signaling negatively regulated by TRIM8; TRIM8 interacts with TRIF and mediates its K6- and K33-linked polyubiquitination, disrupting the TRIF-TBK1 association and terminating TLR3/4-mediated inflammatory responses. TRIM8 KO mice, co-immunoprecipitation, ubiquitination assays, cytokine measurement in vivo Journal of immunology High 28747347
2016 LUBAC components (SHARPIN, HOIL-1, HOIP) interact with the TLR3 signaling complex, enabling TLR3-mediated gene activation; absence of LUBAC increases formation of a TLR3-induced death-inducing signaling complex, leading to enhanced cell death; excessive TLR3-mediated dsRNA-induced cell death is a major contributor to cpdm dermatitis, ameliorated by genetic Tlr3 co-ablation. LUBAC component KO mice, co-immunoprecipitation of TLR3 signaling complex, cpdm/Tlr3 double-KO mice, cell death assays The Journal of experimental medicine High 27810922
2016 TLR3 activation in neurons signals through MYD88 (not cytokines) to suppress Disc1 expression, impairing dendritic arborization; this effect is rescued by MYD88 deficiency or DISC1 overexpression; neonatal TLR3 activation has long-lasting effects on dendritic spine density and morphology. Cultured neurons, in vivo mouse brain electroporation, MYD88-/- rescue, DISC1 overexpression, in utero electroporation EMBO reports Medium 27979975
2016 Zika virus infection of human cerebral organoids upregulates TLR3, and TLR3 inhibition reduces the organoid-size decrease caused by ZIKV; TLR3 activation disrupts neuronal development gene networks including 41 neuronal development genes, linking ZIKV-mediated TLR3 activation to impaired neurogenesis. Human cerebral organoids, ZIKV infection, TLR3 inhibitor treatment, transcriptomic pathway analysis Cell stem cell Medium 27162029
2016 Tumor exosomal RNAs activate TLR3 in alveolar epithelial cells to induce chemokine secretion and neutrophil recruitment, forming a pre-metastatic niche; TLR3-deficient mice show reduced lung metastasis; exosomal RNAs enriched in small nuclear RNAs are the activating ligands. TLR3-/- mice, spontaneous metastasis models, exosome RNA fractionation, lung epithelial cell stimulation assays Cancer cell High 27505671
2016 TLR3 or TLR4 activation of mesenchymal stromal cells enhances regulatory T cell (Treg) induction via Notch signaling; the effect requires cell contact and is associated with increased expression of the Notch ligand Delta-like 1; TLR3/4 gene silencing abolishes the effect. TLR3/4 gene silencing in MSCs, coculture with CD4+ lymphocytes, Notch inhibition, DLL1 expression analysis Stem cells Medium 27571579
2017 TLR3-TRIF signaling promotes autophagy induction in cardiomyocytes via the TRIF-dependent pathway (without affecting autophagic flux); in a mouse model of chronic myocardial infarction, TLR3 KO inhibits autophagy, reduces infarct size, and improves survival; rapamycin abolishes TLR3-KO protection. TLR3 KO mice, myocardial infarction model, LC3-II/p62 western blots, tandem mRFP-GFP-LC3 adenovirus, rapamycin rescue Journal of cellular and molecular medicine Medium 28945004
2017 IL-36γ expression in keratinocytes is induced by dsRNA/TLR3 signaling through activation of TRIF and subsequent induction of the zinc finger protein SLUG, which abrogates the inhibitory effect of vitamin D receptor (VDR) on the IL-36γ gene promoter; IL-36γ then induces REG3A to promote wound re-epithelialization. TLR3/TRIF pathway analysis, SLUG knockdown, VDR reporter assays, wound healing model The Journal of investigative dermatology Medium 28774595
2017 IRF1 and IRF2 drive Tlr3 transcription through binding to the Tlr3 promoter, a process dependent on host cell factor HCFC2; Hcfc2 mutations abolish macrophage responses to poly(I:C) and impair survival during influenza and HSV-1 infection. ENU mutagenesis screen, HCFC2 mutant mice, chromatin immunoprecipitation (IRF1/IRF2 binding to Tlr3 promoter), poly(I:C) cytokine assays The Journal of experimental medicine High 28970238
2018 During HSV-1 infection, TLR3 recruits mTORC2 in neurons and astrocytes, leading to chemokine induction and trafficking of TLR3 to the cell periphery; peripheral TLR3 enables mTORC1 activation required for type I IFN induction; an agonistic anti-TLR3 antibody rescues intracranial HSV-1 infection exacerbated by mTOR inhibition. Co-immunoprecipitation of TLR3-mTORC2, TLR3 trafficking imaging, mTOR inhibitor treatment in vivo, agonistic anti-TLR3 antibody rescue Nature immunology High 30201994
2018 TLR3 activation by dsRNA, independent of inflammation, drives cardiomyocyte maturation via the RelA subunit of NF-κB, which becomes enriched at promoters of cardiomyocyte maturation genes under conditions promoting maturation. TLR3 inhibition during cardiomyocyte differentiation, chromatin immunoprecipitation (RelA at maturation gene promoters), NF-κB pathway analysis Stem cells Medium 29676038
2019 ZCCHC3 positively regulates TLR3-mediated signaling by promoting recruitment of TRIF to TLR3 after poly(I:C) stimulation; ZCCHC3-deficiency markedly inhibits TLR3- but not TLR4-mediated type I IFN and cytokine induction; Zcchc3-/- mice are less susceptible to poly(I:C)-induced inflammatory death. ZCCHC3 knockout mice, Co-IP, overexpression and KO of ZCCHC3, poly(I:C) stimulation assays Journal of molecular cell biology Medium 32133501
2019 ZFYVE1 (a FYVE-domain-containing protein) binds TLR3 via its FYVE domain and TLR3's ectodomain, and increases TLR3 binding affinity for poly(I:C); ZFYVE1 deficiency reduces TLR3-mediated antiviral gene induction, and Zfyve1-/- mice are less susceptible to poly(I:C)-induced inflammatory death. ZFYVE1 KO mice, Co-IP, poly(I:C) binding affinity assays, TLR3-mediated gene induction assays Cellular & molecular immunology Medium 31388100
2020 Tumor-derived dsRNA (including endogenous retroviral element RNAs upregulated in metastatic cells and detected extracellularly) induces endothelial SLIT2 expression via TLR3; endothelial SLIT2 and its receptor ROBO1 then promote cancer cell migration toward endothelial cells and intravasation, driving metastasis. Endothelial ribosome tagging (RiboTag), deep sequencing, Slit2 endothelial conditional KO mice, TLR3 pathway analysis, intravasation assays Nature High 32999457
2020 Shock wave therapy (SWT) promotes spinal cord regeneration via TLR3 in a TLR3-dependent manner; TLR3 stimulation inhibits neuronal degeneration and drives IL-6-dependent recruitment and differentiation of neuronal progenitor cells; tlr3 is also identified as a crucial enhancer of spinal cord regeneration in zebrafish. Tlr3-/- mice, spinal cord injury model, SWT intervention, IL-6 pathway analysis, zebrafish tlr3 model JCI insight Medium 32759498
2021 Human TLR3 controls constitutive (basal) levels of IFNB mRNA and secreted IFN-β protein in fibroblasts and cortical neurons, establishing constitutive ISG expression; TLR3-deficient fibroblasts and cortical neurons are vulnerable to multiple virus families (VSV, HSV-1, and others) due to impaired basal IFN-β immunity. TLR3-deficient human fibroblasts, iPSC-derived cortical neurons, Tlr3-/- mouse embryonic fibroblasts, IFN-β ELISA, ISG qRT-PCR, viral susceptibility assays The Journal of clinical investigation High 33393505
2021 RNase T2 in endosomes/lysosomes negatively regulates TLR3 responses by degrading dsRNA ligands; RNase T2-deficiency upregulates TLR3 responses and impairs TLR7 responses; RNase T2 co-localizes with internalized poly(I:C) in endosomes, and mutants with impaired RNA degradation fail to rescue altered TLR3/TLR7 responses. RNase T2 KO macrophages, confocal co-localization, in vitro RNA degradation assays with RNase T2 mutants, poly(I:C) stimulation International immunology Medium 34161582
2022 Cryo-EM structure of full-length TLR3 complexed with ~400-bp poly(I:C) reveals that TLR3 dimers cluster along the dsRNA helix in a highly organized, cooperative fashion with a uniform inter-dimer spacing of 103 Å; the intracellular and transmembrane domains are dispensable for clustering, suggesting clustering of TLR3 dimers triggers ordered assembly of intracellular signaling adaptors. Cryo-electron microscopy of full-length TLR3 + ~400-bp RNA complex, deletion mutant analysis Nature communications High 36371424
2022 ZBP1 promotes timely delivery of RIPK1 to the TLR3/4 adaptor TRIF and M1-ubiquitination of RIPK1 downstream of TLR3 stimulation, sustaining inflammatory signaling; Zbp1-/- mice exhibit resistance to LPS-induced septic shock with reduced inflammatory responses. ZBP1 KO mice, Co-IP of RIPK1-TRIF complex, ubiquitination assays, in vivo LPS challenge PNAS Medium 35666872
2022 PKR and TLR3 sense long intracellular dsRNA through distinct signals and synergistically induce rapid apoptosis; PKR induces translational arrest reducing cFLIP levels, which then enables TLR3/TRIF-dependent caspase-8 activation; both PKR and TLR3 are essential for viral RNA-mediated apoptosis. Cytoplasmic RNA injection, PKR and TLR3 KO cells, caspase-8 activation assays, cFLIP western blots Cell death & disease Medium 35970851
2023 Cryo-EM analysis of TLR3 with longer dsRNA reveals TLR3 dimers laterally assemble into a higher multimeric complex along the dsRNA, providing the structural basis for cooperative binding and efficient signal transduction; this explains the dsRNA length-dependency of TLR3 activation. Cryo-electron microscopy, TLR3 complex with longer dsRNA, cooperative binding analysis Nature communications High 36631495

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 4755 11607032
2003 Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science (New York, N.Y.) 2496 12855817
2003 IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nature immunology 2220 12692549
2005 Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 1970 16111635
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2001 Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. The Journal of experimental medicine 1457 11561001
1998 A family of human receptors structurally related to Drosophila Toll. Proceedings of the National Academy of Sciences of the United States of America 1291 9435236
1999 Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science (New York, N.Y.) 1195 10426995
1996 Selective interaction of JNK protein kinase isoforms with transcription factors. The EMBO journal 1119 8654373
2004 Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. Journal of immunology (Baltimore, Md. : 1950) 973 15356140
2003 TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction. Nature immunology 927 12539043
2002 Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. Journal of immunology (Baltimore, Md. : 1950) 900 12471095
2007 TLR3 deficiency in patients with herpes simplex encephalitis. Science (New York, N.Y.) 877 17872438
2004 mRNA is an endogenous ligand for Toll-like receptor 3. The Journal of biological chemistry 855 14729660
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2000 Differential expression and regulation of toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 788 10820283
2008 Sequence- and target-independent angiogenesis suppression by siRNA via TLR3. Nature 739 18368052
2011 cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms. Molecular cell 728 21737330
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2002 IRF3 mediates a TLR3/TLR4-specific antiviral gene program. Immunity 680 12354379
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2004 RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nature immunology 641 15064760
2009 Commensal bacteria regulate Toll-like receptor 3-dependent inflammation after skin injury. Nature medicine 587 19966777
2016 Zika Virus Depletes Neural Progenitors in Human Cerebral Organoids through Activation of the Innate Immune Receptor TLR3. Cell stem cell 573 27162029
2008 TLR3: interferon induction by double-stranded RNA including poly(I:C). Advanced drug delivery reviews 564 18262679
2016 Tumor Exosomal RNAs Promote Lung Pre-metastatic Niche Formation by Activating Alveolar Epithelial TLR3 to Recruit Neutrophils. Cancer cell 541 27505671
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2004 Involvement of toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus. The Journal of biological chemistry 521 15579900
2011 The structural biology of Toll-like receptors. Structure (London, England : 1993) 505 21481769
2011 Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines. Journal of immunology (Baltimore, Md. : 1950) 477 21398612
2006 Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells. Nature cell biology 471 17128265
2005 Crystal structure of human toll-like receptor 3 (TLR3) ectodomain. Science (New York, N.Y.) 470 15961631
2010 Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response. Journal of immunology (Baltimore, Md. : 1950) 436 20100933
2012 Ultraviolet radiation damages self noncoding RNA and is detected by TLR3. Nature medicine 328 22772463
2015 Caspase-8 scaffolding function and MLKL regulate NLRP3 inflammasome activation downstream of TLR3. Nature communications 224 26104484
2005 Transcriptional signaling by double-stranded RNA: role of TLR3. Cytokine & growth factor reviews 203 15733829
2010 Study of TLR3, TLR4 and TLR9 in breast carcinomas and their association with metastasis. BMC cancer 194 21129170
2009 Distinct and complementary functions of MDA5 and TLR3 in poly(I:C)-mediated activation of mouse NK cells. The Journal of experimental medicine 173 19995959
2005 TLR3 in antiviral immunity: key player or bystander? Trends in immunology 172 16027039
2021 Toll-like receptor 3 (TLR3) regulation mechanisms and roles in antiviral innate immune responses. Journal of Zhejiang University. Science. B 170 34414698
2006 Microglia recognize double-stranded RNA via TLR3. Journal of immunology (Baltimore, Md. : 1950) 162 16517751
2021 TLR3 and TLR7 RNA Sensor Activation during SARS-CoV-2 Infection. Microorganisms 150 34576716
2011 Antiviral responses induced by the TLR3 pathway. Reviews in medical virology 145 21312311
2015 dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration. Cell stem cell 144 26253200
2009 Activation of TLR3 in the trophoblast is associated with preterm delivery. American journal of reproductive immunology (New York, N.Y. : 1989) 144 19239422
2013 TLR3 immunity to infection in mice and humans. Current opinion in immunology 140 23290562
2012 Age-dependent TLR3 expression of the intestinal epithelium contributes to rotavirus susceptibility. PLoS pathogens 139 22570612
2005 TLR3-induced activation of mast cells modulates CD8+ T-cell recruitment. Blood 138 15840693
2014 Role of extracellular RNA and TLR3-Trif signaling in myocardial ischemia-reperfusion injury. Journal of the American Heart Association 134 24390148
2009 Small interfering RNA-induced TLR3 activation inhibits blood and lymphatic vessel growth. Proceedings of the National Academy of Sciences of the United States of America 128 19359485
2014 TLR3 deficiency in herpes simplex encephalitis: high allelic heterogeneity and recurrence risk. Neurology 126 25339207
2010 Study of TLR3, TLR4, and TLR9 in prostate carcinomas and their association with biochemical recurrence. Cancer immunology, immunotherapy : CII 121 20978888
2020 Tumoural activation of TLR3-SLIT2 axis in endothelium drives metastasis. Nature 117 32999457
2016 TLR3 or TLR4 Activation Enhances Mesenchymal Stromal Cell-Mediated Treg Induction via Notch Signaling. Stem cells (Dayton, Ohio) 117 27571579
2014 Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome. Nature communications 116 24637670
2011 Overexpression of TLR3, TLR4, TLR7 and TLR9 in esophageal squamous cell carcinoma. World journal of gastroenterology 107 21990957
2011 MDA5 and TLR3 initiate pro-inflammatory signaling pathways leading to rhinovirus-induced airways inflammation and hyperresponsiveness. PLoS pathogens 105 21637773
2020 Trial watch: TLR3 agonists in cancer therapy. Oncoimmunology 89 32934877
2021 TLR3 controls constitutive IFN-β antiviral immunity in human fibroblasts and cortical neurons. The Journal of clinical investigation 88 33393505
2015 WDFY1 mediates TLR3/4 signaling by recruiting TRIF. EMBO reports 79 25736436
2016 --LUBAC deficiency perturbs TLR3 signaling to cause immunodeficiency and autoinflammation. The Journal of experimental medicine 77 27810922
2012 TLR3 activation efficiency by high or low molecular mass poly I:C. Innate immunity 75 23035017
2016 Immune biomarkers PD-1/PD-L1 and TLR3 in malignant pleural mesotheliomas. Human pathology 71 26980049
2022 ZBP1 promotes inflammatory responses downstream of TLR3/TLR4 via timely delivery of RIPK1 to TRIF. Proceedings of the National Academy of Sciences of the United States of America 67 35666872
2018 TLR3 agonist and CD40-targeting vaccination induces immune responses and reduces HIV-1 reservoirs. The Journal of clinical investigation 63 30148455
2017 TRIM8 Negatively Regulates TLR3/4-Mediated Innate Immune Response by Blocking TRIF-TBK1 Interaction. Journal of immunology (Baltimore, Md. : 1950) 62 28747347
2017 Chronic ethanol consumption: role of TLR3/TRIF-dependent signaling. Addiction biology 62 28840972
2019 Angiotensin II-induced hypertension and cardiac hypertrophy are differentially mediated by TLR3- and TLR4-dependent pathways. American journal of physiology. Heart and circulatory physiology 59 30793936
2005 TLR3 activation inhibits human mast cell attachment to fibronectin and vitronectin. Molecular immunology 59 16280166
2018 Combating herpesvirus encephalitis by potentiating a TLR3-mTORC2 axis. Nature immunology 58 30201994
2021 TLR3 agonists: RGC100, ARNAX, and poly-IC: a comparative review. Immunologic research 57 34145551
2018 Endosomal TLR3, TLR7, and TLR8 control neuronal morphology through different transcriptional programs. The Journal of cell biology 57 29777026
2015 TLR3 triggering regulates PD-L1 (CD274) expression in human neuroblastoma cells. Cancer letters 57 25697485
2013 Toll-like receptor 3 (TLR3) activation induces microRNA-dependent reexpression of functional RARβ and tumor regression. Proceedings of the National Academy of Sciences of the United States of America 57 23716670
2015 EBV-encoded RNA via TLR3 induces inflammation in nasopharyngeal carcinoma. Oncotarget 55 26172457
2015 Transcriptome sequencing of microglial cells stimulated with TLR3 and TLR4 ligands. BMC genomics 54 26159724
2015 TLR3 agonist and Sorafenib combinatorial therapy promotes immune activation and controls hepatocellular carcinoma progression. Oncotarget 54 26287667
2014 TLR3 and MDA5 signalling, although not expression, is impaired in asthmatic epithelial cells in response to rhinovirus infection. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 54 24131248
2015 TLR3 drives IRF6-dependent IL-23p19 expression and p19/EBI3 heterodimer formation in keratinocytes. Immunology and cell biology 50 26303210
2017 IL-36γ Induced by the TLR3-SLUG-VDR Axis Promotes Wound Healing via REG3A. The Journal of investigative dermatology 49 28774595
2016 TLR3 Agonist Poly-IC Induces IL-33 and Promotes Myelin Repair. PloS one 49 27022724
2014 Polymorphisms in the TLR3 gene are associated with risk for type 1 diabetes mellitus. European journal of endocrinology 47 24408902
2013 Association of TLR2, TLR3, TLR4 and CD14 genes polymorphisms with oral cancer risk and survival. Oral diseases 46 23796347
2012 TLR3/TICAM-1 signaling in tumor cell RIP3-dependent necroptosis. Oncoimmunology 45 23162759
2015 Interferon-Gamma Enhances TLR3 Expression and Anti-Viral Activity in Keratinocytes. The Journal of investigative dermatology 44 25822580
2017 LncRNA CRNDE triggers inflammation through the TLR3-NF-κB-Cytokine signaling pathway. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 42 28621230
2022 TLR3 forms a highly organized cluster when bound to a poly(I:C) RNA ligand. Nature communications 41 36371424
2016 Apolipoproteins L control cell death triggered by TLR3/TRIF signaling in dendritic cells. European journal of immunology 41 27198486
2008 Signal regulatory protein alpha negatively regulates both TLR3 and cytoplasmic pathways in type I interferon induction. Molecular immunology 40 18471880
2017 TLR4 signaling induces TLR3 up-regulation in alveolar macrophages during acute lung injury. Scientific reports 39 28198368
2017 Functional failure of TLR3 and its signaling components contribute to herpes simplex encephalitis. Journal of neuroimmunology 39 29305044
2016 TLR3 downregulates expression of schizophrenia gene Disc1 via MYD88 to control neuronal morphology. EMBO reports 39 27979975
2023 TLR3 forms a laterally aligned multimeric complex along double-stranded RNA for efficient signal transduction. Nature communications 37 36631495
2018 Cardiomyocyte Maturation Requires TLR3 Activated Nuclear Factor Kappa B. Stem cells (Dayton, Ohio) 37 29676038
2009 Inflammatory regulation by TLR3 in acute hepatitis. Journal of immunology (Baltimore, Md. : 1950) 36 19710451
2023 Extracellular RNAs-TLR3 signaling contributes to cognitive impairment after chronic neuropathic pain in mice. Signal transduction and targeted therapy 35 37544956
2019 A Toll-like receptor 3 (TLR3) agonist ARNAX for therapeutic immunotherapy. Advanced drug delivery reviews 34 31302192
2015 Regulation of TLR3 Activation by S100A9. Journal of immunology (Baltimore, Md. : 1950) 34 26385519
2009 Characterization of equine and other vertebrate TLR3, TLR7, and TLR8 genes. Immunogenetics 34 19568743
2019 MiR-146a down-regulates inflammatory response by targeting TLR3 and TRAF6 in Coxsackievirus B infection. RNA (New York, N.Y.) 32 31676570
2017 TLR3 contributes to persistent autophagy and heart failure in mice after myocardial infarction. Journal of cellular and molecular medicine 32 28945004
2013 TRIF-mediated TLR3 and TLR4 signaling is negatively regulated by ADAM15. Journal of immunology (Baltimore, Md. : 1950) 32 23365087
2009 TLR3 gene polymorphisms and liver disease manifestations in chronic hepatitis C. Journal of medical virology 32 19475618
2023 A novel defined TLR3 agonist as an effective vaccine adjuvant. Frontiers in immunology 31 36761735
2015 Both MicroRNA-155 and Virus-Encoded MiR-155 Ortholog Regulate TLR3 Expression. PloS one 31 25938551
2014 FAAH-mediated modulation of TLR3-induced neuroinflammation in the rat hippocampus. Journal of neuroimmunology 31 25245162
2012 A TRIF-independent branch of TLR3 signaling. Journal of immunology (Baltimore, Md. : 1950) 31 22323545
2021 Inborn errors of TLR3- or MDA5-dependent type I IFN immunity in children with enterovirus rhombencephalitis. The Journal of experimental medicine 30 34726731
2017 Association of TLR3 L412F Polymorphism with Cytomegalovirus Infection in Children. PloS one 28 28046022
2009 TLR3 in human eosinophils: functional effects and decreased expression during allergic rhinitis. International archives of allergy and immunology 28 19752565
2020 ZCCHC3 modulates TLR3-mediated signaling by promoting recruitment of TRIF to TLR3. Journal of molecular cell biology 27 32133501
2018 FAAH inhibition attenuates TLR3-mediated hyperthermia, nociceptive- and anxiety-like behaviour in female rats. Behavioural brain research 26 29953903
2018 TLR2 and TLR3 expression as a biomarker for the risk of doxorubicin-induced heart failure. Toxicology letters 26 29959987
2015 Necrosis-induced TLR3 Activation Promotes TLR2 Expression in Gingival Cells. Journal of dental research 26 26045329
2023 The effect of TLR3 priming conditions on MSC immunosuppressive properties. Stem cell research & therapy 25 38031182
2014 Cellular stress amplifies TLR3/4-induced CXCL1/2 gene transcription in mononuclear phagocytes via RIPK1. Journal of immunology (Baltimore, Md. : 1950) 25 24920846
2014 Scavenger receptor SREC-I promotes double stranded RNA-mediated TLR3 activation in human monocytes. Immunobiology 25 25641411
2018 TRIM56 Suppresses Multiple Myeloma Progression by Activating TLR3/TRIF Signaling. Yonsei medical journal 24 29214775
2014 Discordant biological and toxicological species responses to TLR3 activation. The American journal of pathology 24 24486326
2020 Shock waves promote spinal cord repair via TLR3. JCI insight 22 32759498
2015 Toll-like receptor 3 (TLR3) and the development of type 1 diabetes mellitus. Archives of endocrinology and metabolism 22 25926108
2014 Mannan binding lectin attenuates double-stranded RNA-mediated TLR3 activation and innate immunity. FEBS letters 22 24530528
2012 Association of TLR3-hyporesponsiveness and functional TLR3 L412F polymorphism with recurrent herpes labialis. Human immunology 22 22537752
2022 PKR and TLR3 trigger distinct signals that coordinate the induction of antiviral apoptosis. Cell death & disease 20 35970851
2021 Contemporary evolution of the innate immune receptor gene TLR3 in an isolated vertebrate population. Molecular ecology 20 33949028
2018 ACTG1 and TLR3 are biomarkers for alcohol-associated hepatocellular carcinoma. Oncology letters 20 30675230
2017 HCFC2 is needed for IRF1- and IRF2-dependent Tlr3 transcription and for survival during viral infections. The Journal of experimental medicine 20 28970238
2012 TLR3 dsRNA agonist inhibits growth and invasion of HepG2.2.15 HCC cells. Oncology reports 19 22552584
2021 Skewed endosomal RNA responses from TLR7 to TLR3 in RNase T2-deficient macrophages. International immunology 18 34161582
2019 The zinc-finger protein ZFYVE1 modulates TLR3-mediated signaling by facilitating TLR3 ligand binding. Cellular & molecular immunology 18 31388100