Affinage

TLR8

Toll-like receptor 8 · UniProt Q9NR97

Length
1041 aa
Mass
119.8 kDa
Annotated
2026-04-28
100 papers in source corpus 46 papers cited in narrative 46 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TLR8 is an endosomal pattern-recognition receptor that senses single-stranded RNA from viruses, bacteria, protozoa, and endogenous sources to initiate innate immune responses predominantly in monocytes, myeloid dendritic cells, and neutrophils. The receptor is proteolytically processed by furin-like convertases and cathepsins at an insertion loop between LRR14 and LRR15, trafficked to early endosomes by UNC93B1, and recognizes UR/URR sequence motifs in ssRNA; ligand binding induces conformational rearrangement of the preformed homodimer, activating a MyD88→IRAK→MEKK3→NF-κB and MAPK (Erk1/2, p38) signaling cascade that is TAK1-independent, driving production of TNF-α, IL-12, IL-1β, and type I IFNs, with CXCL4 co-stimulation repurposing TBK1-IKKε toward IRF5-dependent inflammatory gene activation and NLRP3 inflammasome engagement (PMID:16737960, PMID:25297876, PMID:22164301, PMID:18322178, PMID:35701499). TLR8 escapes X-chromosome inactivation, resulting in higher expression in female monocytes, and exerts a cell-intrinsic restraint on TLR7-driven autoimmunity in dendritic cells; gain-of-function TLR8 mutations cause childhood-onset immunodeficiency with neutropenia and bone marrow failure (PMID:37723501, PMID:24474776, PMID:33512449). TLR8 also drives macrophage pro-inflammatory polarization in response to microbial small RNAs carried on LDL particles, contributing to atherosclerotic plaque inflammation (PMID:36474072).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2000 Medium

    Establishing TLR8 as an X-linked innate immune receptor with NF-κB-activating capacity answered the basic question of whether this orphan TLR paralog was a functional signaling receptor.

    Evidence Molecular cloning and NF-κB reporter assays in transfected cells

    PMID:11022120

    Open questions at the time
    • No endogenous ligand identified
    • No pathway components defined
    • Cell-type expression pattern not established
  2. 2005 High

    Demonstrating that TLR8 agonists selectively activate myeloid DCs and monocytes (TNF-α, IL-12) while TLR7 agonists activate pDCs (IFN-α) resolved the question of whether TLR7 and TLR8 had redundant or distinct cellular functions.

    Evidence Selective synthetic TLR7 vs TLR8 agonists tested on purified human immune cell subsets with cytokine ELISA

    PMID:15661881

    Open questions at the time
    • Natural RNA ligand not yet identified
    • Structural basis for selectivity unknown
  3. 2006 High

    Dissection of the signaling cascade showed TLR8 uses a TAK1-independent, MEKK3-dependent pathway to activate NF-κB via IKKγ phosphorylation without IκBα degradation, establishing a unique signaling mode among TLRs.

    Evidence TAK1−/− and MEKK3−/− MEFs, IRAK-deficient cells, kinase-dead mutants, NF-κB reporter and Western blot

    PMID:16737960

    Open questions at the time
    • Whether MEKK3-dependence holds in primary myeloid cells not confirmed
    • Downstream transcription factor targets not mapped
  4. 2008 High

    Identification of UR/URR ssRNA motifs as species-specific TLR8 ligands answered what natural nucleic acid sequences are recognized and explained why rodent TLR8 appeared nonfunctional with standard ligands.

    Evidence HEK-TLR transfection NF-κB reporter with synthetic ssRNA motifs, cytokine ELISA across human, bovine, and murine cells

    PMID:18322178

    Open questions at the time
    • Crystal structure of RNA-bound TLR8 not yet available
    • Mechanism of species selectivity not structurally resolved
  5. 2009 High

    Deletion mutagenesis pinpointed a five-amino-acid motif following LRR-14 as essential for ligand responsiveness but dispensable for dimerization, separating ligand recognition from receptor assembly.

    Evidence Multi-species alignment, deletion mutagenesis with NF-κB reporter in HEK-TLR transfectants

    PMID:20004021

    Open questions at the time
    • Structural mechanism of the LRR14-15 insertion in ligand recognition unclear
    • Role in proteolytic processing not yet linked
  6. 2010 High

    Transcriptional regulation of TLR8 was defined: C/EBPδ and C/EBPβ drive basal transcription, while IFN-γ/STAT1 enhances it via GAS elements, explaining how inflammatory stimuli amplify TLR8 expression.

    Evidence TLR8 promoter reporter assays and ChIP for C/EBPδ, C/EBPβ, and STAT1 binding

    PMID:20829351

    Open questions at the time
    • Whether estrogen-driven STAT1 upregulation is quantitatively important in vivo
    • Epigenetic regulation of TLR8 locus not addressed
  7. 2011 High

    Multiple studies established TLR8 trafficking and processing requirements: UNC93B1 physically associates with TLR8 for endosomal delivery; TLR8 resides in early endosomes/ER; and TLR8 activates HIV latency reversal via Erk1/2 and p38→NF-κB in myeloid cells with paracrine TNF-α acting on CD4+ T cells.

    Evidence Co-IP for UNC93B1-TLR8 interaction, confocal microscopy, tail-truncation mutagenesis, kinase inhibitors, conditioned media HIV reactivation assays

    PMID:21357269 PMID:22164301

    Open questions at the time
    • Whether UNC93B1 is rate-limiting for TLR8 surface delivery in vivo
    • Structural basis for UNC93B1-TLR8 interaction unknown
  8. 2013 High

    Overexpression of human TLR8 in transgenic mice caused spontaneous autoimmune inflammation of pancreas, salivary glands, and joints, establishing that TLR8 gain-of-function is sufficient for autoimmunity via DC-intrinsic co-stimulatory upregulation.

    Evidence Multiple-copy huTLR8 transgenic mice with dose-dependent phenotype, FACS for DC co-stimulatory molecules, collagen-induced arthritis model

    PMID:24277153

    Open questions at the time
    • Whether specific RNA ligands drive autoimmunity in transgenic mice not identified
    • Human relevance of gene-dosage effect not established
  9. 2014 High

    Proteolytic processing of TLR8 by furin-like convertases and cathepsins at the LRR14-15 insertion loop was shown to be required for functional receptor, linking the earlier mutagenesis finding to a stepwise endosomal maturation mechanism; separately, TLR8→NF-κB was shown to prime pro-IL-1β, with NLRP3 inflammasome required for IL-1β maturation during HIV infection.

    Evidence Protease inhibitors, Western blot for cleavage fragments, endosomal fractionation, LRR deletion mutants; TLR8 siRNA plus NLRP3/cathepsin B inhibitors for inflammasome studies

    PMID:24939850 PMID:25297876

    Open questions at the time
    • Precise cleavage sites not mapped at amino acid resolution
    • Whether processing regulates ligand specificity not tested
  10. 2014 High

    TLR8 was shown to restrain TLR7-mediated autoimmunity in a DC-intrinsic manner (complementing TLR9's restraint of TLR7 in B cells), establishing TLR8 as a negative regulator of TLR7.

    Evidence TLR8−/−, TLR9−/−, TLR8/9−/− double KO mice with cell-type-specific cytokine and autoantibody readouts

    PMID:24474776

    Open questions at the time
    • Molecular mechanism by which TLR8 suppresses TLR7 signaling in DCs not fully defined
    • Whether human TLR8 exerts the same restraint
  11. 2015 High

    TLR8 was established as the primary human sensor for bacterial RNA (S. aureus, E. coli, S. pyogenes, Borrelia) and the functional equivalent of mouse TLR13, recognizing UR/URR motifs; 2'-O-methylation of bacterial tRNA antagonizes TLR8 at the RNA-binding site, revealing a bacterial immune evasion mechanism.

    Evidence CRISPR/RNAi KO THP-1 cells, complementation, synthetic modified ORNs, live bacterial infection in primary monocyte-derived macrophages

    PMID:25823462 PMID:26101323 PMID:26545385

    Open questions at the time
    • Full repertoire of bacterial RNA modifications that evade TLR8 not catalogued
    • Crystal structure of RNA-bound TLR8 not yet solved
  12. 2015 High

    Crystal structures of the TLR8 ectodomain with imidazoquinoline agonists revealed the small-molecule binding site and enabled structure-guided design of a 20-fold more potent agonist, providing the first atomic-resolution view of TLR8 ligand recognition.

    Evidence X-ray crystallography of hTLR8 ectodomain complexes, SAR medicinal chemistry, HEK-TLR reporter assay

    PMID:26351878

    Open questions at the time
    • RNA-bound crystal structure still missing
    • Conformational dynamics of activation not captured
  13. 2017 High

    Crystal structures of TLR8 with small-molecule antagonists revealed a unique protein-protein interface pocket on the preformed homodimer; antagonists stabilize the resting dimer state, establishing a novel allosteric inhibition mechanism distinct from competitive agonist displacement.

    Evidence X-ray crystallography of TLR8-antagonist complexes, functional assays in cell lines, primary cells, and huTLR8-transgenic splenocytes

    PMID:29155428

    Open questions at the time
    • Whether antagonist pocket exists in other TLR family members
    • In vivo pharmacokinetic and therapeutic validation incomplete
  14. 2018 High

    TLR8-dependent bacterial RNA sensing was linked to TFH cell differentiation via IL-12 family cytokines, connecting innate TLR8 signaling to adaptive humoral immunity; a hypermorphic TLR8 polymorphism conferred protective BCG vaccine responses in humans.

    Evidence TLR8 agonist stimulation of APCs, live vs. dead bacterial immunization in pigs, human BCG vaccination cohort genetic analysis

    PMID:29556002

    Open questions at the time
    • Exact mechanism by which TLR8 polymorphism enhances vaccine immunity not defined
    • Whether TLR8-driven TFH response is generalizable across vaccines
  15. 2021 High

    Gain-of-function TLR8 mutations were identified as the cause of childhood-onset immunodeficiency with neutropenia and bone marrow failure, establishing TLR8 as a Mendelian disease gene; somatic mosaicism was sufficient for the phenotype.

    Evidence iPSC-derived myeloid functional assays, WES/WGS across six patients with three distinct variants, immune phenotyping

    PMID:33512449

    Open questions at the time
    • How increased TLR8 signaling causes bone marrow failure mechanistically
    • Whether loss-of-function TLR8 variants cause immunodeficiency
  16. 2022 High

    CXCL4 was shown to synergize with TLR8 by repurposing TBK1-IKKε toward IRF5 (not IRF3/7), activating de novo enhancers and the NLRP3 inflammasome, providing a mechanistic explanation for CXCL4-amplified inflammatory pathology in diseases like SSc.

    Evidence TBK1/IKKε inhibitors, IRF5 siRNA, ATAC-seq and H3K27ac ChIP-seq, NLRP3 inhibitor, co-stimulation assays in primary monocytes

    PMID:35701499

    Open questions at the time
    • Whether CXCL4 acts via a specific surface receptor to reach TBK1
    • In vivo validation of combined CXCL4-TLR8 pathway inhibition
  17. 2022 High

    Microbial small RNAs carried on LDL particles were identified as endogenous TLR8 ligands driving macrophage pro-inflammatory polarization in atherosclerotic plaques; competitive TLR8 antagonism with locked nucleic acids reduced plaque burden in vivo.

    Evidence LDL reconstitution ± msRNA cargo, TLR8 locked nucleic acid antagonist, scRNA-seq of lesion macrophages, multiple mouse atherosclerosis models

    PMID:36474072

    Open questions at the time
    • Source and diversity of msRNAs on human LDL not fully characterized
    • Long-term therapeutic safety of TLR8 antagonism in atherosclerosis unknown
  18. 2023 High

    TLR8 was demonstrated to escape X-chromosome inactivation in monocytes and CD4+ T cells, with biallelic expression in women and Klinefelter men, providing a molecular basis for sex-biased innate immune responses.

    Evidence RNA FISH for primary TLR8 transcripts relative to X-chromosome territories, Western blot and flow cytometry across defined genotype groups

    PMID:37723501

    Open questions at the time
    • Whether XCI escape of TLR8 is tissue-specific beyond monocytes and T cells
    • Functional consequence of biallelic expression on disease susceptibility not quantified in prospective studies

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution crystal structure of TLR8 bound to its natural ssRNA ligand is still lacking, and the precise conformational mechanism by which RNA binding triggers homodimer rearrangement and TIR domain activation remains structurally undefined.
  • No RNA-bound TLR8 crystal structure
  • Mechanism coupling ectodomain conformational change to TIR domain signaling not resolved
  • In vivo therapeutic validation of TLR8-specific antagonists in autoimmune or cardiometabolic disease models is incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0003723 RNA binding 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005768 endosome 4 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-168256 Immune System 13 R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 4
Partners
IRAK4IRF5MEKK3MYD88SOCS1TBK1UNC93B1
Complex memberships
TLR8 homodimer

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 TLR8 contains an ectodomain with multiple leucine-rich repeats and a cytoplasmic TIR domain homologous to the IL-1 receptor; expression of constitutively active TLR8 stimulates NF-κB signaling. TLR8 gene is located on the X chromosome. Molecular cloning, NF-κB reporter assay in transfected cells European cytokine network Medium 11022120
2005 TLR7 and TLR8 have distinct cell-type selectivities: TLR8 agonists directly activate myeloid dendritic cells, monocytes, and monocyte-derived DCs, inducing TNF-α, IL-12, and MIP-1α, whereas TLR7 agonists preferentially activate plasmacytoid DCs and induce IFN-α. Selective synthetic small-molecule TLR7 or TLR8 agonists, cytokine ELISA, purified human immune cell subsets Journal of immunology High 15661881
2006 TLR8-mediated NF-κB and JNK activation is IRAK-dependent but does not require IRAK kinase activity or TAK1; it is uniquely dependent on MEKK3, which drives IKKγ phosphorylation and IκBα phosphorylation without IκBα degradation—a signaling mode distinct from IL-1R/TLR4. Genetic KO MEFs (TAK1−/−, MEKK3−/−), IRAK-deficient human 293 cells, kinase-inactive mutants, NF-κB reporter, Western blot for IKK and IκBα The Journal of biological chemistry High 16737960
2006 TLR7 and TLR8 activation of NK cells occurs indirectly: TLR8 agonists require IL-18 and IL-12p70 for IFN-γ induction, whereas TLR7 agonists require type I IFN for CD69 upregulation. Purified NK cells lack TLR7/TLR8 expression and do not respond directly to these agonists. Purified human NK cells, cytokine blockade experiments, PBMC cultures, in vivo mouse NK cytotoxicity assays International immunology High 16728430
2006 Poly(T) oligodeoxynucleotides (ODNs) physically interact with imidazoquinolines and can modulate TLR7/TLR8 signaling: poly(T) ODNs inhibit TLR7 and enhance TLR8 NF-κB activation and cytokine production in a manner dependent on co-presence in the same cellular compartment. HEK-NF-κB reporter assay with TLR transfectants, cytokine ELISA in primary PBMC, physical interaction assay between ODNs and IRMs Journal of immunology Medium 17114492
2008 Specific single-stranded RNA sequence motifs (containing UR/URR motifs) selectively activate human TLR8 but not TLR7, producing Th1-like and proinflammatory cytokines from monocytes and myeloid DCs; rodent TLR8 fails to respond to these ligands, indicating species-specific recognition. HEK-TLR transfection NF-κB reporter, cytokine ELISA from primary human, bovine, murine immune cells; TLR7-expressing pDC assays Journal of immunology High 18322178
2008 TLR7 and TLR8 activate distinct signaling pathways for human DC maturation: both engage JNK and NF-κB for CCR7/CD86/CD83/CD40 and IL-6/IL-12p40 upregulation; p38MAPK positively regulates TLR7 responses but inhibits CD40 and IL-12 in TLR8-stimulated DCs; JAK/STAT participates in TLR7 but negatively regulates TLR8 responses. Selective TLR7 (imiquimod) or TLR8 (3M002) agonists, specific kinase inhibitors, cytokine ELISA, flow cytometry for DC maturation markers Journal of leukocyte biology Medium 19164127
2009 A five-amino-acid motif in the TLR8 ectodomain (immediately following LRR-14) is essential for species-specific ligand recognition; deletion of this motif abrogates ligand responsiveness; the motif is not required for self-dimerization or intracellular localization. Multi-species TLR8 sequence alignment, deletion mutagenesis, NF-κB reporter assay in TLR-transfected HEK cells Molecular immunology High 20004021
2009 LL37 binds self-RNA released by dying cells, protects it from extracellular degradation, and transports it into endosomal compartments of myeloid DCs (mDCs), where it activates TLR8 to produce TNF-α and IL-6 and promote mDC maturation. Confocal microscopy, TLR7/TLR8-blocking antibodies and siRNA, ELISA for cytokines, mDC maturation markers by flow cytometry The Journal of experimental medicine High 19703986
2010 HIV-1 activates NF-κB through TLR8 to initiate transcription of integrated provirus by RNA polymerase II in dendritic cells; DC-SIGN signaling via Raf-1-dependent phosphorylation of NF-κB p65 at Ser276 additionally recruits pTEF-b to enable transcription elongation and full-length viral transcripts. siRNA knockdown, pharmacological inhibitors, ChIP, Western blot for RNAPII phosphorylation, HIV replication assays in primary DCs Nature immunology High 20364151
2010 TLR8 is activated in human monocytic cells following Helicobacter pylori phagocytosis; the rs3764880 SNP (Met1Val) modulates translation of two TLR8 isoforms (v1 and v2), with TLR8v2 being the predominant functional form; TLR8v1 positively regulates TLR8 function in CD16+CD14+ monocytes. Bacterial phagocytosis assay, siRNA knockdown, NF-κB reporter, isoform-specific expression constructs, flow cytometry Human mutation Medium 20652908
2011 UNC93B1 physically associates with human TLR8 (similar to TLR3/7/9) and is required for TLR8-mediated signaling. TLR8 localizes to the early endosome and ER (not late endosome/lysosome) in human monocytes; the transmembrane domain and TIR domain are required for proper endosomal targeting. Co-immunoprecipitation, confocal microscopy, tail-truncation mutagenesis, NF-κB reporter assay, subcellular fractionation PloS one High 22164301
2011 TLR8 activates HIV from latently infected myeloid-monocytic cells via the MAPK pathway (Erk1/2 and p38α → NF-κB); TNF-α secreted downstream of TLR8 acts autocrinally on latently infected myeloid cells and paracrinally on neighboring latently infected CD4+ T cells (which lack TLR8) to activate HIV. Kinase inhibitors (Erk1/2, p38α, JNK), Western blot, HIV replication/latency reversal assays, conditioned media transfer experiments Journal of immunology High 21357269
2011 Antiphospholipid antibodies induce translocation of TLR8 from the ER to the endosome in human monocytes via endosomal NADPH oxidase activation and superoxide generation, sensitizing cells to TLR8 ligands. mRNA expression, confocal microscopy for TLR8 localization, NADPH oxidase inhibitors, flow cytometry Blood Medium 21734241
2011 DCIR (an ITIM-containing C-type lectin) is internalized via clathrin-dependent endocytosis in human DCs and, upon triggering, selectively inhibits TLR8-mediated IL-12 and TNF-α production without affecting TLR2/3/4-induced cytokines, demonstrating CLR/TLR8 crosstalk. DCIR-specific mAb triggering, cytokine ELISA, clathrin inhibition, confocal microscopy for co-localization with LAMP-1 Journal of leukocyte biology Medium 19028959
2013 Human TLR8 recognizes Borrelia burgdorferi RNA (not DNA) in the phagosome of human monocytes, colocalizing with internalized bacterial RNA in both early (EEA1+) and late (LAMP1+) endosomes; TLR8 drives IRF7-dependent IFN-β transcription via the MyD88 pathway, distinct from TLR2-mediated NF-κB responses. siRNA knockdown of TLR8, confocal microscopy (co-localization of TLR8 with phagosomally delivered RNA), cytokine ELISA, IRAK-4-deficient monocytes, PEI-mediated RNA delivery to phagosome Journal of leukocyte biology High 23906644
2013 Transgenic mice expressing human TLR8 develop spontaneous inflammation targeting pancreas, salivary glands, and joints; huTLR8 signaling exerts a DC-intrinsic effect upregulating co-stimulatory molecules and driving T cell activation, resulting in autoimmune diseases distinct from TLR7-driven pathology. Human TLR8 transgenic mice (multiple copy number lines), collagen-induced arthritis model, FACS for DC co-stimulatory markers, cytokine measurement The Journal of experimental medicine High 24277153
2014 TLR8 on dendritic cells restrains TLR7-mediated autoimmunity in mice: TLR8-deficient DCs are hyperresponsive to TLR7 ligand, while TLR9 restrains TLR7 response specifically in B cells, demonstrating additive but cell-type-distinct control of TLR7 by TLR8 (on DCs) and TLR9 (on B cells). TLR8−/−, TLR9−/−, TLR8/9−/− double KO mice on C57BL/6, cell-type specific cytokine and autoantibody readouts, FACS Proceedings of the National Academy of Sciences High 24474776
2014 TLR8 proteolytic processing in human monocytes and macrophages involves furin-like proprotein convertase and cathepsins acting in early/late endosomes; the insertion loop between LRR14 and LRR15 is indispensable for cleavage and stepwise processing of the N-terminal fragment, required for functional receptor. Protease inhibitors (furin, cathepsin), Western blot for TLR8 cleavage fragments, endosomal fractionation, LRR deletion mutants, primary human monocyte analysis Journal of immunology High 25297876
2014 HIV-1 infection induces pro-IL-1β expression in human monocytes via TLR8-mediated NF-κB activation; maturation and release of IL-1β then requires NLRP3 inflammasome activation, with cathepsin B and reactive oxygen species critical for inflammasome activation; HIV-1-derived RNA is sufficient to trigger both steps. TLR8 siRNA knockdown, NLRP3 inhibitors, cathepsin B inhibitors, ROS scavengers, HIV entry/RT/integration inhibitors, ELISA for IL-1β The Journal of biological chemistry High 24939850
2014 TLR8 signaling in AML cells promotes myeloid differentiation and growth inhibition in a TLR8/MyD88/p38-dependent manner; TLR8 agonists impair AML growth in immunodeficient mice via direct anti-leukemic effects independent of immune modulation. TLR8 agonist treatment of AML cells, siRNA/shRNA knockdown, p38 inhibitors, MyD88 inhibition, xenograft mouse model, differentiation marker FACS Leukemia Medium 25283842
2015 Human TLR8 senses bacterial RNA from S. aureus, E. coli, and S. pyogenes, as well as mitochondrial 16S rRNA-derived oligoribonucleotides, recognizing UR/URR sequence motifs; TLR8 is the functional human equivalent of mouse TLR13; Unc93b1−/− and Tlr8−/− THP-1 cells are unresponsive, while ectopic TLR8 confers responsiveness. CRISPR/RNAi-based Unc93b1−/− and Tlr8−/− THP-1 cell lines, overexpression complementation, synthetic ORNs, bacterial RNA stimulation, cytokine ELISA EMBO reports High 26545385
2015 Human TLR8 is the primary receptor for bacterial RNA in human monocytes/macrophages, including response to Streptococcus pyogenes infection; TLR8-sensed sequence motifs are distinct from TLR13-recognized sequences; TLR8-dependent detection is critical for monocyte activation by intact streptococci. siRNA knockdown and overexpression in primary monocyte-derived macrophages, TLR8-specific blocking, cytokine ELISA (IL-6, TNF, IFN-β), live bacterial infection assay Journal of immunology High 26101323
2015 2'-O-methylation at position Gm18 of bacterial tRNA inhibits TLR8 (and TLR7) activation by competing with stimulatory RNA for receptor binding; the antagonistic effect was specific for RNA and did not inhibit small-molecule TLR7/8 agonist R848, demonstrating competition at the RNA-binding site. Synthetic 2'-O-methylated RNA oligonucleotides, primary human monocyte stimulation, MAP kinase and NF-κB signaling assays, competition binding inference Journal of innate immunity Medium 25823462
2015 A single naturally occurring 2'-O-methylation in an 18S rRNA-derived RNA sequence abolishes TLR7 activation while preserving TLR8 activation, converting a dual TLR7/TLR8 ligand into a TLR8-specific ligand; 2'-O-deoxy and 2'-fluoro substitutions lack this selective effect. TLR-deficient pDC analysis, HEK293 genetic complementation assays, synthetic RNA with defined chemical modifications, IFN-α and IL-6 cytokine readouts PloS one High 25785446
2015 Crystal structures of the hTLR8 ectodomain co-crystallized with two regioisomers of N1-substituted imidazoquinolines revealed the agonist binding site and subtle differences in molecular contacts; structure-guided design based on these interactions yielded a novel TLR8 agonist ~20-fold more potent than the parent compound. X-ray crystallography of hTLR8 ectodomain complexes, structure-activity relationship medicinal chemistry, HEK-TLR reporter assay, rabbit immunization adjuvanticity model Journal of medicinal chemistry High 26351878
2016 TLR8 and TLR7 activate distinct signaling cascades in human monocytes during RNA virus infection: TLR7 specifically induces FOSL1 transcription factor expression that reduces IL-27 and TNFα production, and TLR7 (but not TLR8) stimulates Ca2+ flux that inhibits type I IFN responses. Selective TLR agonists, siRNA knockdown, Ca2+ flux imaging, cytokine multiplex assays, transcriptomic analysis of virus-infected monocytes Science signaling High 31662487
2016 Estrogen promotes STAT1 expression via an estrogen response element, and STAT1 then binds IFN-γ activated sequence (GAS) elements in the TLR8 promoter to drive TLR8 transcriptional upregulation; miR-21 within extracellular vesicles can act as an endogenous TLR8 ligand triggering cytokine production. Luciferase reporter assay with TLR8 promoter, ChIP for STAT1 binding, EV-encapsulated miR-21 stimulation of TLR8, cytokine ELISA Clinical immunology Medium 28039018
2016 Mouse TLR8 physically associates with SOCS-1 (but TLR7 does not), coupling TLR8 to SOCS-1-mediated suppression of TLR7-dependent antiviral IFN responses; siRNA knockdown of SOCS-1 increased ISG-56 and TLR7 expression after WNV infection. Co-immunoprecipitation of TLR8 with SOCS-1, Tlr8−/− mice, siRNA knockdown of SOCS-1, WNV infection model, RT-PCR for ISGs Journal of immunology Medium 27798161
2016 IFNα enhances TLR8-stimulated IL-6 production from human neutrophils by increasing endogenous TNFα production; this TNFα acts in an autocrine manner to induce IκBζ co-activator and enhance C/EBPβ recruitment to the IL-6 promoter. The effect is not due to IFNα-induced TLR7 co-activation. TNFα neutralizing antibody, C/EBPβ ChIP, Western blot for IκBζ, TLR7-specific control experiments, cytokine ELISA in highly purified neutrophils and SLE patient cells Scientific reports Medium 26790609
2017 Crystal structures identified a unique binding site on the TLR8 homodimer protein-protein interface; small-molecule antagonists binding this site stabilize the preformed TLR8 dimer in its resting (inactive) state, preventing receptor activation—a distinct mechanism from competitive agonist displacement. X-ray crystallography of TLR8-antagonist complexes, functional assays in cell lines, primary human cells, and huTLR8-transgenic mouse splenocytes Nature chemical biology High 29155428
2018 TLR8-dependent detection of bacterial RNA by antigen-presenting cells drives a specific cytokine profile (IL-12 family) that promotes follicular helper T (TFH) cell differentiation; a hypermorphic TLR8 polymorphism was associated with protective BCG vaccine-induced immunity in humans; live bacteria stimulate TFH via TLR8, whereas dead bacteria do not. TLR8 agonist stimulation of human and porcine APCs, TLR8 genetic polymorphism analysis, live vs. heat-killed bacterial immunization in pigs, human BCG vaccination cohort study Nature immunology High 29556002
2018 Plasmacytoid DCs in SSc patients aberrantly express TLR8 (not seen in healthy donors); TLR8 on pDCs drives CXCL4 secretion via PI3Kδ; CXCL4 potentiates TLR8- and TLR9-induced IFN production. Transgenic mice expressing TLR8 show exacerbated scleroderma with pDC recruitment to fibrotic skin. Human pDC characterization, PI3Kδ inhibitor, TLR8-transgenic mice, pDC-depleting antibodies in mouse scleroderma model, cytokine ELISA Science translational medicine High 29321259
2018 X-ray crystallography guided rational design of picomolar-potency TLR8 antagonists that target the homodimer protein-protein interface pocket; two crystal structures validated the binding contacts; these inhibitors suppressed TLR8 inflammatory signaling in cell lines, PBMCs, and huTLR8-transgenic mouse splenocytes. X-ray crystallography (two structures), structure-activity relationship chemistry, NF-κB reporter, cytokine ELISA in primary cells and patient specimens Cell chemical biology High 30100350
2018 TLR8, TLR7, and TLR3 promote dendritic pruning of mouse neurons via MYD88 signaling, but TLR8 specifically activates MAPK signaling for dendritic pruning and is more critical for dendritic arborization at late development stages in vivo; TLR8 does not control axonal growth (unlike TLR7/TLR3). In vitro neuronal cultures, in utero electroporation, TLR-specific agonists, transcriptomic profiling, pathway inhibitor studies (MAPK), MYD88 signaling requirement The Journal of cell biology Medium 29777026
2019 TLR8 senses RNA from Plasmodium falciparum-infected red blood cells (not TLR7 or TLR9), triggering IFN-γ production in NK cells uniquely via IL-12p70 and bioactive IL-18 release from monocytes; this represents the first identification of protozoan RNA as a TLR8 ligand. Primary human immune cell stimulation with iRBC and purified iRBC RNA, TLR-blocking antibodies, ELISA for IFN-γ/IL-12/IL-18, NK cell IFN-γ readout Frontiers in immunology Medium 30972055
2019 TLR8 activation in human neutrophils induces IL-23 (IL-12B + IL-23A subunits) but not IL-12 via chromatin remodeling; this requires endogenous TNF-α; TLR8-activated neutrophil supernatants drive Th17 cell differentiation from naïve T cells in an IL-23-dependent manner. Highly pure neutrophil isolation, RNA-seq, ChIP-seq for chromatin remodeling, TNF-α neutralizing antibody, ELISA, naïve T cell Th17 polarization assay Journal of leukocyte biology High 30817049
2019 TLR8 ligation in CD4+ T cells boosts TCR signaling and promotes Th1/Th17 differentiation; endosomal HIV RNA activates cytokine production from CD4+ T cells in a TLR8-specific manner (not TLR7/TLR9); TLR8 engagement enhances HIV-1 replication and latency reversal in patient-derived T cells. TLR-selective agonists, siRNA knockdown, endosomal HIV uptake assays, TCR signaling assays, latency reversal in patient-derived cells, cytokine multiplex Nature communications High 31919342
2020 Rationally designed triazole derivative TH1027 specifically inhibits TLR8 by binding between two TLR8 monomers at an unconventional protein-protein interface pocket, as validated by X-ray crystallography; TH1027 dose-dependently suppresses TLR8-mediated inflammation in monocyte cell lines, PBMCs, and RA patient specimens. X-ray crystallography, NF-κB reporter, cytokine ELISA in THP-1, primary PBMCs, and RA patient specimens Journal of medicinal chemistry High 32233366
2021 Gain-of-function variants in TLR8 cause childhood-onset immunodeficiency with neutropenia, lymphoproliferation, B-cell defects, and bone marrow failure; myeloid cells from patient iPSCs show increased TLR8 responsiveness; somatic mosaicism in TLR8 is sufficient to produce the dominant phenotype. iPSC-derived myeloid differentiation, functional NF-κB/cytokine assays with TLR8 agonists, immune phenotyping by flow cytometry, whole exome/genome sequencing, serum cytokine measurement Blood High 33512449
2022 CXCL4 signaling synergizes with TLR8 in human monocytes to activate TBK1 and IKKε, which are repurposed toward an inflammatory response via coupling with IRF5 (not IRF3/7), activating the NLRP3 inflammasome and inducing de novo enhancers associated with inflammatory genes via chromatin remodeling. Co-stimulation with CXCL4 + TLR8 agonist, TBK1/IKKε inhibitors, IRF5 siRNA, ATAC-seq and H3K27ac ChIP-seq for epigenomic remodeling, NLRP3 inhibitor, IL-1β ELISA Nature communications High 35701499
2022 Microbial small RNAs (msRNA) enriched on LDL activate macrophage TLR8 to drive pro-inflammatory polarization and cytokine secretion; competitive TLR8 antagonism with locked nucleic acids prevents native LDL-induced macrophage polarization in vitro and reorganizes lesion macrophage phenotypes in vivo, reducing atherosclerotic disease burden. LDL reconstitution with/without msRNA cargo, TLR8 competitive antagonist (locked nucleic acids), scRNA-seq of lesion macrophages, multiple mouse atherosclerosis models, cytokine ELISA Nature cell biology High 36474072
2022 A novel germline TLR8 p.G572V mutation impairs TLR8 protein stability, causes cross-reactivity to TLR7 ligands, and reduces TLR8's ability to restrain TLR7 signaling, leading to increased NF-κB activation and IL-1β/IL-6/TNFα production; TLR7 inhibition effectively treated the resulting autoimmune/autoinflammatory disease. Transfection of mutant TLR8 in cell lines, primary cell functional assays, NF-κB reporter, cytokine ELISA, TLR7 inhibitor treatment American journal of hematology High 34981838
2023 TLR8 escapes X chromosome inactivation (XCI) in human monocytes and CD4+ T cells; cells harboring simultaneous TLR7 and TLR8 transcript foci are sevenfold more frequent in women and Klinefelter syndrome men than euploid men; TLR8 protein expression is significantly higher in female monocyte subsets. RNA FISH for primary TLR8 transcripts relative to X chromosome territories, Western blot, flow cytometry for TLR8 protein in monocyte subsets from women, KS men, and euploid men Biology of sex differences High 37723501
2010 TLR8 promoter regulation requires C/EBPδ and C/EBPβ via three C/EBP cis-acting elements for basal transcription; TLR8 agonist R848 stimulation enhances C/EBPδ binding (not C/EBPβ) to increase TLR8 transcriptional activity; IFN-γ increases TLR8 transcription via STAT1 binding to GAS elements in the TLR8 promoter. TLR8 promoter isolation, luciferase reporter assay, ChIP for C/EBPδ, C/EBPβ, and STAT1 binding The Journal of biological chemistry High 20829351
2017 TLR4 and TLR8 can form a heterodimer at the endosome, as demonstrated by immunoprecipitation with TLR8-targeted antibodies pulling down TLR4 and confirmed by confocal co-localization; heterodimerization increases upon TLR8 stimulation and induces IL-12p40, NF-κB, and IRF3 signaling. Co-immunoprecipitation with TLR8-specific antibodies + mass spectrometry, confocal microscopy co-localization, NF-κB/IRF3 reporter assays, docking models International journal of molecular sciences Medium 33557133

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. The Journal of experimental medicine 578 19703986
2005 Synthetic TLR agonists reveal functional differences between human TLR7 and TLR8. Journal of immunology (Baltimore, Md. : 1950) 562 15661881
2000 Cloning and characterization of a sub-family of human toll-like receptors: hTLR7, hTLR8 and hTLR9. European cytokine network 321 11022120
2008 Identification of RNA sequence motifs stimulating sequence-specific TLR8-dependent immune responses. Journal of immunology (Baltimore, Md. : 1950) 254 18322178
2008 TLR7 and TLR8 as targets in cancer therapy. Oncogene 245 18176600
2010 HIV-1 exploits innate signaling by TLR8 and DC-SIGN for productive infection of dendritic cells. Nature immunology 217 20364151
2019 Lactate modulates CD4+ T-cell polarization and induces an immunosuppressive environment, which sustains prostate carcinoma progression via TLR8/miR21 axis. Oncogene 206 30664688
2012 TLR8: the forgotten relative revindicated. Cellular & molecular immunology 206 23085951
2018 Plasmacytoid dendritic cells promote systemic sclerosis with a key role for TLR8. Science translational medicine 183 29321259
2008 The use of TLR7 and TLR8 ligands for the enhancement of cancer immunotherapy. The oncologist 177 18701762
2013 RNA recognition by human TLR8 can lead to autoimmune inflammation. The Journal of experimental medicine 156 24277153
2011 VTX-2337 is a novel TLR8 agonist that activates NK cells and augments ADCC. Clinical cancer research : an official journal of the American Association for Cancer Research 146 22128302
2014 HIV-1 infection induces interleukin-1β production via TLR8 protein-dependent and NLRP3 inflammasome mechanisms in human monocytes. The Journal of biological chemistry 141 24939850
2014 TLR8 signaling enhances tumor immunity by preventing tumor-induced T-cell senescence. EMBO molecular medicine 140 25231413
2006 The small antitumoral immune response modifier imiquimod interacts with adenosine receptor signaling in a TLR7- and TLR8-independent fashion. The Journal of investigative dermatology 135 16575388
2019 TLR7 and TLR8 activate distinct pathways in monocytes during RNA virus infection. Science signaling 133 31662487
2006 Distinct indirect pathways govern human NK-cell activation by TLR-7 and TLR-8 agonists. International immunology 131 16728430
2008 Association analysis identifies TLR7 and TLR8 as novel risk genes in asthma and related disorders. Thorax 124 18682521
2018 Recognition of microbial viability via TLR8 drives TFH cell differentiation and vaccine responses. Nature immunology 121 29556002
2008 DCIR is endocytosed into human dendritic cells and inhibits TLR8-mediated cytokine production. Journal of leukocyte biology 114 19028959
2017 Small-molecule inhibition of TLR8 through stabilization of its resting state. Nature chemical biology 107 29155428
2014 TLR8 on dendritic cells and TLR9 on B cells restrain TLR7-mediated spontaneous autoimmunity in C57BL/6 mice. Proceedings of the National Academy of Sciences of the United States of America 102 24474776
2009 Identification and characterization of TLR8 and MyD88 homologs in Atlantic salmon (Salmo salar). Developmental and comparative immunology 95 19422846
2011 Antiphospholipid antibodies induce translocation of TLR7 and TLR8 to the endosome in human monocytes and plasmacytoid dendritic cells. Blood 94 21734241
2009 TLR7 and TLR8 agonists trigger different signaling pathways for human dendritic cell maturation. Journal of leukocyte biology 94 19164127
2014 Novel HIV-1 miRNAs stimulate TNFα release in human macrophages via TLR8 signaling pathway. PloS one 91 25191859
2009 A five-amino-acid motif in the undefined region of the TLR8 ectodomain is required for species-specific ligand recognition. Molecular immunology 89 20004021
2020 Trial Watch: experimental TLR7/TLR8 agonists for oncological indications. Oncoimmunology 84 32934889
2006 TLR8-mediated NF-kappaB and JNK activation are TAK1-independent and MEKK3-dependent. The Journal of biological chemistry 84 16737960
2021 Therapeutic Potential of TLR8 Agonist GS-9688 (Selgantolimod) in Chronic Hepatitis B: Remodeling of Antiviral and Regulatory Mediators. Hepatology (Baltimore, Md.) 83 33368377
2015 Human TLR8 senses UR/URR motifs in bacterial and mitochondrial RNA. EMBO reports 83 26545385
2007 TLR8: an innate immune receptor in brain, neurons and axons. Cell cycle (Georgetown, Tex.) 78 18000403
2008 Inhibitors of TLR8 reduce TNF production from human rheumatoid synovial membrane cultures. Journal of immunology (Baltimore, Md. : 1950) 76 19017992
2016 IFNα enhances the production of IL-6 by human neutrophils activated via TLR8. Scientific reports 75 26790609
2021 Immunodeficiency and bone marrow failure with mosaic and germline TLR8 gain of function. Blood 74 33512449
2006 Oligodeoxynucleotides differentially modulate activation of TLR7 and TLR8 by imidazoquinolines. Journal of immunology (Baltimore, Md. : 1950) 74 17114492
2008 RNA recognition via TLR7 and TLR8. Handbook of experimental pharmacology 72 18071655
2015 TLR8 Senses Bacterial RNA in Human Monocytes and Plays a Nonredundant Role for Recognition of Streptococcus pyogenes. Journal of immunology (Baltimore, Md. : 1950) 71 26101323
2008 Analysis of the neuroinflammatory response to TLR7 stimulation in the brain: comparison of multiple TLR7 and/or TLR8 agonists. Journal of immunology (Baltimore, Md. : 1950) 70 18490763
2020 Sensing of HIV-1 by TLR8 activates human T cells and reverses latency. Nature communications 69 31919342
2014 Endosomal localization of TLR8 confers distinctive proteolytic processing on human myeloid cells. Journal of immunology (Baltimore, Md. : 1950) 69 25297876
2017 Phase Ib Study of Immune Biomarker Modulation with Neoadjuvant Cetuximab and TLR8 Stimulation in Head and Neck Cancer to Overcome Suppressive Myeloid Signals. Clinical cancer research : an official journal of the American Association for Cancer Research 67 29061643
2013 Human TLR8 is activated upon recognition of Borrelia burgdorferi RNA in the phagosome of human monocytes. Journal of leukocyte biology 65 23906644
2017 The Human-Associated Archaeon Methanosphaera stadtmanae Is Recognized through Its RNA and Induces TLR8-Dependent NLRP3 Inflammasome Activation. Frontiers in immunology 63 29181003
2010 Genetic modulation of TLR8 response following bacterial phagocytosis. Human mutation 63 20652908
2013 The ultra-potent and selective TLR8 agonist VTX-294 activates human newborn and adult leukocytes. PloS one 59 23483986
2021 Glucose metabolism characteristics and TLR8-mediated metabolic control of CD4+ Treg cells in ovarian cancer cells microenvironment. Cell death & disease 58 33414414
2015 TNF-α Induced by Hepatitis C Virus via TLR7 and TLR8 in Hepatocytes Supports Interferon Signaling via an Autocrine Mechanism. PLoS pathogens 58 26023919
2018 Endosomal TLR3, TLR7, and TLR8 control neuronal morphology through different transcriptional programs. The Journal of cell biology 57 29777026
2011 UNC93B1 physically associates with human TLR8 and regulates TLR8-mediated signaling. PloS one 54 22164301
2014 The role of TLR8 signaling in acute myeloid leukemia differentiation. Leukemia 53 25283842
2015 2'-O-Methylation within Bacterial RNA Acts as Suppressor of TLR7/TLR8 Activation in Human Innate Immune Cells. Journal of innate immunity 52 25823462
2011 TLR8 activates HIV from latently infected cells of myeloid-monocytic origin directly via the MAPK pathway and from latently infected CD4+ T cells indirectly via TNF-α. Journal of immunology (Baltimore, Md. : 1950) 51 21357269
2008 Porcine TLR8 and TLR7 are both activated by a selective TLR7 ligand, imiquimod. Molecular immunology 48 18439678
2011 VTX-1463, a novel TLR8 agonist for the treatment of allergic rhinitis. Expert opinion on investigational drugs 47 21548830
2018 Small-Molecule TLR8 Antagonists via Structure-Based Rational Design. Cell chemical biology 46 30100350
2016 Estrogen-regulated STAT1 activation promotes TLR8 expression to facilitate signaling via microRNA-21 in systemic lupus erythematosus. Clinical immunology (Orlando, Fla.) 46 28039018
2011 Inhibition of TLR8- and TLR4-induced Type I IFN induction by alcohol is different from its effects on inflammatory cytokine production in monocytes. BMC immunology 45 21962237
2015 Structure-Based Design of Human TLR8-Specific Agonists with Augmented Potency and Adjuvanticity. Journal of medicinal chemistry 44 26351878
2022 Safety and efficacy of the oral TLR8 agonist selgantolimod in individuals with chronic hepatitis B under viral suppression. Journal of hepatology 42 38133554
2016 HCV RNA Activates APCs via TLR7/TLR8 While Virus Selectively Stimulates Macrophages Without Inducing Antiviral Responses. Scientific reports 42 27385120
2019 Human neutrophils activated via TLR8 promote Th17 polarization through IL-23. Journal of leukocyte biology 40 30817049
2014 Functional polymorphisms of TLR8 are associated with hepatitis C virus infection. Immunology 40 24205871
2023 TLR8 escapes X chromosome inactivation in human monocytes and CD4+ T cells. Biology of sex differences 39 37723501
2020 LncRNA TLR8-AS1 promotes metastasis and chemoresistance of ovarian cancer through enhancing TLR8 mRNA stability. Biochemical and biophysical research communications 37 32278547
2009 Cancer immunotherapeutic potential of novel small molecule TLR7 and TLR8 agonists. Journal of immunotoxicology 37 19848448
2016 Microparticles derived from obese adipose tissue elicit a pro-inflammatory phenotype of CD16+, CCR5+ and TLR8+ monocytes. Biochimica et biophysica acta. Molecular basis of disease 36 27677832
2022 CXCL4 synergizes with TLR8 for TBK1-IRF5 activation, epigenomic remodeling and inflammatory response in human monocytes. Nature communications 35 35701499
2017 TLR7 Deficiency Leads to TLR8 Compensative Regulation of Immune Response against JEV in Mice. Frontiers in immunology 34 28265274
2015 Granzyme B expression is enhanced in human monocytes by TLR8 agonists and contributes to antibody-dependent cellular cytotoxicity. Journal of immunology (Baltimore, Md. : 1950) 34 25667415
2009 High-frequency haplotypes in the X chromosome locus TLR8 are associated with both CD and UC in females. Inflammatory bowel diseases 34 18942751
2009 Characterization of equine and other vertebrate TLR3, TLR7, and TLR8 genes. Immunogenetics 34 19568743
2007 Differentiation of primary adult microglia alters their response to TLR8-mediated activation but not their capacity as APC. Glia 34 17823968
2021 Safety, Pharmacokinetics, and Pharmacodynamics of the Oral TLR8 Agonist Selgantolimod in Chronic Hepatitis B. Hepatology (Baltimore, Md.) 33 33704806
2016 Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemoimmunotherapy. Clinical cancer research : an official journal of the American Association for Cancer Research 32 27702821
2021 African Swine Fever Virus A528R Inhibits TLR8 Mediated NF-κB Activity by Targeting p65 Activation and Nuclear Translocation. Viruses 31 34696476
2010 C/EBP{delta} and STAT-1 are required for TLR8 transcriptional activity. The Journal of biological chemistry 31 20829351
2017 Identification of High-Potency Human TLR8 and Dual TLR7/TLR8 Agonists in Pyrimidine-2,4-diamines. Journal of medicinal chemistry 30 28146629
2022 LDL delivery of microbial small RNAs drives atherosclerosis through macrophage TLR8. Nature cell biology 29 36474072
2019 Human TLR8 Senses RNA From Plasmodium falciparum-Infected Red Blood Cells Which Is Uniquely Required for the IFN-γ Response in NK Cells. Frontiers in immunology 29 30972055
2013 Evidence for a detrimental role of TLR8 in ischemic stroke. Experimental neurology 29 24196452
2016 Functional polymorphisms of the TLR7 and TLR8 genes contribute to Mycobacterium tuberculosis infection. Tuberculosis (Edinburgh, Scotland) 28 27156628
2019 p53-responsive TLR8 SNP enhances human innate immune response to respiratory syncytial virus. The Journal of clinical investigation 27 31430261
2014 HIV-derived ssRNA binds to TLR8 to induce inflammation-driven macrophage foam cell formation. PloS one 27 25090652
2019 The Bacterial Product Violacein Exerts an Immunostimulatory Effect Via TLR8. Scientific reports 26 31541142
2016 Increased adipose tissue expression of TLR8 in obese individuals with or without type-2 diabetes: significance in metabolic inflammation. Journal of inflammation (London, England) 26 27980459
2017 The anticancer effect of mebendazole may be due to M1 monocyte/macrophage activation via ERK1/2 and TLR8-dependent inflammasome activation. Immunopharmacology and immunotoxicology 25 28472897
2009 TLR8-mediated activation of human monocytes inhibits TL1A expression. European journal of immunology 25 19637197
2022 TLR8/TLR7 dysregulation due to a novel TLR8 mutation causes severe autoimmune hemolytic anemia and autoinflammation in identical twins. American journal of hematology 24 34981838
2017 TLR8 ligation induces apoptosis of monocytic myeloid-derived suppressor cells. Journal of leukocyte biology 24 29345064
2015 A single naturally occurring 2'-O-methylation converts a TLR7- and TLR8-activating RNA into a TLR8-specific ligand. PloS one 24 25785446
2020 Target-Based Identification and Optimization of 5-Indazol-5-yl Pyridones as Toll-like Receptor 7 and 8 Antagonists Using a Biochemical TLR8 Antagonist Competition Assay. Journal of medicinal chemistry 23 32786235
2021 Follicular Helper T (TFH) Cell Targeting by TLR8 Signaling For Improving HBsAg-Specific B Cell Response In Chronic Hepatitis B Patients. Frontiers in immunology 22 34512670
2020 Rationally Designed Small-Molecule Inhibitors Targeting an Unconventional Pocket on the TLR8 Protein-Protein Interface. Journal of medicinal chemistry 22 32233366
2016 TLR8 Couples SOCS-1 and Restrains TLR7-Mediated Antiviral Immunity, Exacerbating West Nile Virus Infection in Mice. Journal of immunology (Baltimore, Md. : 1950) 22 27798161
2013 Identification, expression profiling of a grass carp TLR8 and its inhibition leading to the resistance to reovirus in CIK cells. Developmental and comparative immunology 22 23632252
2021 Interaction of TLR4 and TLR8 in the Innate Immune Response against Mycobacterium Tuberculosis. International journal of molecular sciences 21 33557133
2014 The dysfunctional innate immune response triggered by Toll-like receptor activation is restored by TLR7/TLR8 and TLR9 ligands in cutaneous lichen planus. The British journal of dermatology 21 24976336
2015 TLR8 gene polymorphism and association in bacterial load in southern Punjab of Pakistan: an association study with pulmonary tuberculosis. International journal of immunogenetics 20 25572425
2016 Imiquimod induces ER stress and Ca(2+) influx independently of TLR7 and TLR8. Biochemical and biophysical research communications 19 27003259