Affinage

TREM1

Triggering receptor expressed on myeloid cells 1 · UniProt Q9NP99

Length
234 aa
Mass
26.4 kDa
Annotated
2026-06-10
100 papers in source corpus 43 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TREM-1 is a myeloid cell-surface immunoreceptor that amplifies innate inflammatory responses by partnering with the ITAM-bearing adapter DAP12, which it constitutively associates with and requires to transduce signals driving cytokine and chemokine production, reactive oxygen species generation, degranulation and phagocytosis (PMID:18192027, PMID:23108097). Receptor activation is triggered by ligand-induced clustering: the TREM-1 ectodomain homooligomerizes in a concentration-dependent manner, DAP12 stabilizes surface expression and multimerization, and the degree of aggregation scales with Ca2+ flux, ROS, and cytokine output (PMID:29568119). Downstream of DAP12, TREM-1 recruits SYK and signals through PI3K/AKT, PLC, p38MAPK and ERK to amplify inflammation, frequently in physical and functional cooperation with the TLR4/LPS receptor complex with which it co-localizes (PMID:20375613, PMID:21393102, PMID:31324751, PMID:32899943). Through these axes TREM-1 converges on NF-κB and the NLRP3/caspase-1 inflammasome, and engages metabolic reprogramming via PI3K/AKT/mTOR-driven HIF-1α accumulation and glycolysis to license inflammasome activation and M1 macrophage polarization (PMID:36594089, PMID:34719965, PMID:38177990). TREM-1 also couples to multiple regulated cell-death programs, including GSDMD-dependent pyroptosis, mTOR/DRP1/RIPK3-dependent necroptosis, and PERK-ER-stress-dependent ferroptosis (PMID:31324751, PMID:36879273, PMID:39461708). Across disease models, genetic deletion or peptide blockade (LR12, LP17) of TREM-1 attenuates pathology in myocardial infarction, atherosclerosis, abdominal aortic aneurysm, liver fibrosis, stroke, and Alzheimer's disease, where it additionally governs microglial bioenergetics and amyloid-β handling (PMID:25840803, PMID:28007141, PMID:27762264, PMID:30137027, PMID:31263278, PMID:33258804, PMID:38539014, PMID:27670763). Soluble TREM-1 is released into plasma during acute inflammatory injury (PMID:25840803).

Mechanistic history

Synthesis pass · year-by-year structured walk · 35 steps
  1. 2007 High

    Established the core signaling architecture: how a receptor lacking intrinsic signaling motifs transduces activation into inflammatory output.

    Evidence Biochemical and functional assays in monocytes and neutrophils showing constitutive TREM-1/DAP12 association and DAP12 phosphorylation-dependent effector functions

    PMID:18192027 PMID:23108097

    Open questions at the time
    • Endogenous physiological ligand not identified
    • Stoichiometry of the TREM-1/DAP12 complex not resolved
  2. 2007 Medium

    Provided early evidence for a cellular TREM-1 ligand, addressing what physically engages the receptor to amplify neutrophil responses.

    Evidence Recombinant TREM-1 fusion protein binding to platelets and TREM-1 blockade in platelet/PMN co-culture

    PMID:17452516

    Open questions at the time
    • Molecular identity of the platelet ligand not defined
    • Single lab; binding shown only with a fusion protein
  3. 2009 Medium

    Defined the proximal kinase requirements for TREM-1-induced oxidative burst and its synergy with TLR4.

    Evidence Pharmacological inhibitors of PI3K/PLC/p38MAPK and Western blot of AKT/ERK phosphorylation in human PMN

    PMID:20375613

    Open questions at the time
    • Inhibitor-based; direct kinase substrates not mapped
    • Relative ordering of PI3K, PLC and MAPK arms unresolved
  4. 2011 Medium

    Showed TREM-1 is physically and functionally integrated with the TLR4 receptor complex, explaining its amplification of LPS responses.

    Evidence Reciprocal blocking antibodies and co-localization immunofluorescence in human neutrophils

    PMID:21393102

    Open questions at the time
    • Co-localization does not prove direct binary interaction
    • Single lab, primary cells only
  5. 2015 High

    Established TREM-1 as a causal driver of inflammatory tissue injury in vivo, moving beyond correlation in cardiac disease.

    Evidence Trem-1 knockout plus LR12 pharmacological inhibition in myocardial infarction models with imaging and functional readouts

    PMID:25840803

    Open questions at the time
    • Cell type responsible (neutrophil vs monocyte) not isolated
    • Trigger for TREM-1 upregulation in ischemic myocardium undefined
  6. 2016 High

    Defined a pro-atherogenic role and a concrete mechanism via CD36 upregulation and foam-cell formation.

    Evidence Two independent Trem1/Apoe double-KO models, bone marrow chimeras, and LR12 blockade with histology and gene expression

    PMID:27762264 PMID:28007141

    Open questions at the time
    • Direct link between TREM-1 signaling and CD36 transcription not mapped
    • Dyslipidemic serum factors that synergize with TREM-1 not identified
  7. 2016 High

    Revealed a beneficial, phagocytic role in CNS by showing TREM1 drives microglial clearance of amyloid-β.

    Evidence Trem1 knockdown/overexpression and agonist antibody in primary microglia and APP/PSEN1 mice with behavioral testing

    PMID:27670763

    Open questions at the time
    • Reconciliation with later detrimental microglial roles unresolved
    • Receptor coupling to phagocytic machinery not detailed
  8. 2018 High

    Resolved the activation mechanism: TREM-1 is switched on by ectodomain oligomerization/clustering rather than monomeric ligation.

    Evidence Native mass spectrometry of ectodomain plus Ca2+/ROS/cytokine assays in monocytes and neutrophils; LR12 limits multimerization

    PMID:29568119

    Open questions at the time
    • Atomic structure of the oligomer not solved
    • Endogenous clustering ligand still unknown
  9. 2018 High

    Demonstrated a cell-autonomous Kupffer cell role for TREM-1 in liver injury and stellate cell activation.

    Evidence Trem1 KO with Kupffer cell reconstitution in CCl4 chronic liver injury model

    PMID:30137027

    Open questions at the time
    • Direct signal from Kupffer cells to stellate cells not defined
  10. 2018 Medium

    Linked TREM-1 to autophagy and ER stress (UPR) regulation in intestinal inflammation.

    Evidence LR12 and Trem-1 KO in DSS colitis with Western blots of autophagy/UPR markers and microbiota sequencing

    PMID:28961797

    Open questions at the time
    • Causal direction between UPR markers and inflammation correlative
    • Single lab, marker-level readouts
  11. 2019 Medium

    Identified SYK as a direct interactor coupling TREM-1 to CARD9/NF-κB and NLRP3/GSDMD-driven pyroptosis in microglia.

    Evidence Co-IP of TREM-1/SYK plus pathway Western blots in MCAO model and microglial cultures with LP17 inhibition

    PMID:31324751

    Open questions at the time
    • Co-IP without reciprocal/structural validation
    • Whether SYK binding is DAP12-mediated not shown
  12. 2019 High

    Established a gut-brain inflammatory axis whereby stroke-induced intestinal TREM1 drives barrier breakdown and bacterial translocation.

    Evidence Genetic KO, pharmacological inhibition, and anti-TREM1 PET imaging in MCAO stroke model

    PMID:31263278

    Open questions at the time
    • Signal inducing intestinal TREM1 beyond noradrenergic input incomplete
  13. 2019 High

    Showed a context-dependent pro-survival role: TREM1 maintains mitochondrial integrity to protect HIV-infected macrophages from apoptosis.

    Evidence TREM1 siRNA in HIV-infected macrophages with BCL2-family Western blots, membrane potential, cytochrome c and caspase-9 readouts

    PMID:31719184

    Open questions at the time
    • How TREM1 controls BCL2-family balance mechanistically unclear
    • siRNA only; no in vivo confirmation
  14. 2019 High

    Defined a mechanism for TREM-1 control of neutrophil chemotaxis via AKT-driven NOX2 superoxide production.

    Evidence Trem1 KO neutrophils with EPR superoxide measurement, oxygen consumption, migration assays and AKT Western blot

    PMID:30667543

    Open questions at the time
    • Direct link between NOX2 superoxide and directional migration not fully separated from AKT
  15. 2019 Medium

    Connected TREM-1 to NET formation through eCIRP-induced ICAM-1+ neutrophils and Rho GTPase activation.

    Evidence TREM-1 KO and LP17 with rmCIRP, flow cytometry, Rho activation and NET quantification

    PMID:32506691

    Open questions at the time
    • Whether eCIRP binds TREM-1 directly not established
    • Single lab
  16. 2020 Medium

    Showed TREM-1 activation induces ER stress via the IRE-1α/XBP-1s arm to amplify cytokine production.

    Evidence Agonist antibody plus IRE-1α inhibitor and XBP-1 silencing in macrophages and LPS-ALI model

    PMID:33957479

    Open questions at the time
    • Mechanism linking surface receptor to UPR sensors unknown
    • Single lab
  17. 2020 Medium

    Identified WARS1 as an upstream inducer of TREM-1 acting through TLR2/TLR4-MyD88/TRIF, and confirmed the DAP12-SYK-AKT signaling loop.

    Evidence TLR/MyD88/TRIF KO cells, TREM-1 knockdown and SYK inhibitor with phosphoprotein Western blots

    PMID:32899943

    Open questions at the time
    • Whether WARS1 acts as a TREM-1 ligand or only an inducer unclear
  18. 2020 Medium

    Demonstrated TREM-1 drives microglial pyroptosis through NLRP3 inflammasome activation after subarachnoid hemorrhage.

    Evidence Recombinant TREM-1 and LP17 antagonist in SAH model with GSDMD-N/IL-1β Western blots

    PMID:32862402

    Open questions at the time
    • Pharmacological-only manipulation; no genetic KO
    • Single lab
  19. 2021 High

    Showed TREM-1 orchestrates AngII-driven Ly6Chi monocyte trafficking and aneurysm formation via CD62L upregulation.

    Evidence Apoe-/-Trem1-/- mice, LR12 blockade and agonist antibody in AngII-AAA model

    PMID:33258804

    Open questions at the time
    • Direct link between AT1R and TREM-1 activation undefined
  20. 2021 Medium

    Placed TREM-1 on the STAT3/HIF-1α axis governing M1 versus M2 macrophage polarization.

    Evidence Trem1 knockdown/overexpression in RAW264.7, Trem1 KO mice and RNA-seq in periodontitis lesions

    PMID:34719965

    Open questions at the time
    • Direct TREM-1 to STAT3 coupling not demonstrated
  21. 2021 Medium

    Identified a TREM-1 role in leukemic transformation, acting downstream or parallel to the DNA damage response in Fanconi anemia pre-LSCs.

    Evidence Trem1 shRNA in Fanca-/- pre-LSCs with transplantation and survival analysis

    PMID:27568523

    Open questions at the time
    • Effector pathway driving pre-LSC expansion unidentified
    • shRNA knockdown only
  22. 2022 Medium

    Established metabolic reprogramming as the link between TREM-1 and inflammasome activation via PI3K/AKT/mTOR-HIF-1α-glycolysis.

    Evidence Agonist antibody with mTOR, HIF-1α and glycolysis (2-DG) inhibitors plus glucose consumption assays in LPS-ALI model

    PMID:36594089

    Open questions at the time
    • Inhibitor-based; direct metabolic flux mapping limited
  23. 2022 Medium

    Implicated TREM-1 in cardiomyocyte pyroptosis through a SMC4/NEMO-NLRP3 axis in sepsis.

    Evidence Co-IP of TREM-1/SMC4 and siRNA in HL-1 cells with LR12 in CLP sepsis model

    PMID:36181338

    Open questions at the time
    • Co-IP without reciprocal validation
    • How a myeloid receptor functions in cardiomyocytes unclear
  24. 2022 Medium

    Extended TREM-1 function beyond immune cells, showing it drives alveolar epithelial cell senescence in pulmonary fibrosis.

    Evidence Agonist antibody and LR12 in MLE12 cells and bleomycin model with senescence-marker Western blots

    PMID:36330909

    Open questions at the time
    • Mechanism of epithelial TREM-1 expression and signaling undefined
  25. 2022 Medium

    Defined endothelial TREM-1 signaling through SYK/β-catenin controlling blood-brain barrier junction proteins after hemorrhage.

    Evidence LP17, SYK-activation CRISPR and SYK inhibitor R406 in ICH model with junction-protein Western blots

    PMID:37170484

    Open questions at the time
    • Connection between SYK and β-catenin not mechanistically detailed
  26. 2022 Medium

    Extended the eCIRP-TREM-1 axis to renal endothelial cells driving acute kidney injury.

    Evidence TREM-1 KO and M3 inhibitory peptide with rmCIRP in mice and human renal endothelial cells

    PMID:36246143

    Open questions at the time
    • Direct eCIRP-TREM-1 binding not shown
    • Single lab
  27. 2023 Medium

    Linked TREM-1 to macrophage necroptosis via mTOR-dependent DRP1 phosphorylation and RIPK3.

    Evidence Agonist antibody with rapamycin, Mdivi-1 and GSK872 in macrophages and LPS-ALI model; DRP1Ser616 Western blots

    PMID:36879273

    Open questions at the time
    • Inhibitor-based; how TREM-1 engages mTOR-DRP1 directly unknown
  28. 2023 Medium

    Connected lipid droplet accumulation to TREM1 buildup, impaired lipophagy, and NLRP3-driven neuroinflammation in diabetic microglia.

    Evidence Co-IP/co-localization of LDs and TREM1 with LP17 in db/db and HFD/STZ models

    PMID:37204119

    Open questions at the time
    • Nature of LD-TREM1 association not defined
    • Pharmacological-only manipulation
  29. 2023 Medium

    Showed TREM1 promotes gastric cancer progression by driving NET-mediated M2 macrophage polarization.

    Evidence TREM1 KO/knock-in mice with DNase-1 epistasis in MNNG-induced gastric cancer model

    PMID:38151453

    Open questions at the time
    • Signal linking TREM1 to NET induction in tumors undefined
  30. 2023 Medium

    Defined an upstream regulatory cascade in which HIV Tat induces microglial TREM1 via TLR4/TICAM1/COX-2/PGE2.

    Evidence TREM1 siRNA with TLR4 blocking and COX-2/PGE2 inhibitors in HIV-infected human microglia

    PMID:37326481

    Open questions at the time
    • Whether silencing-induced death reflects loss of survival signaling unclear
  31. 2023 Medium

    Provided therapeutic proof-of-concept that TREM1 agonism reprograms myeloid cells and drives antitumor immunity.

    Evidence Afucosylated anti-TREM1 agonist antibody (PY159) with cytokine, costimulation and T-cell assays plus syngeneic tumor models

    PMID:37647386

    Open questions at the time
    • Mechanism distinguishing beneficial vs pathogenic TREM1 activation context-dependent
  32. 2024 High

    Established that TREM1 governs age- and amyloid-dependent microglial metabolism and cognitive decline, validated in human AD brain.

    Evidence Trem1 KO and haploinsufficiency in 5XFAD and APPSwe mice with metabolomics, bioenergetics, transcriptomics, PET and postmortem IHC

    PMID:38539014

    Open questions at the time
    • Reconciliation with the earlier phagocytosis-promoting role in AD unresolved
  33. 2024 Medium

    Reinforced TREM1 control of M1 polarization and NF-κB-dependent NLRP3 activation in microglia in chronic migraine.

    Evidence TREM1 knockdown/overexpression with NF-κB inhibitor PDTC in BV2 cells and NTG migraine model with LR12

    PMID:38177990

    Open questions at the time
    • Direct receptor-to-NF-κB coupling not isolated
  34. 2024 Medium

    Showed hypoxia/HIF-1α-induced TREM1 in glioblastoma TAMs promotes glioma stem cell mesenchymal states via TGFβ2/SMAD signaling.

    Evidence HIF-1α ChIP, TREM1 overexpression/knockdown, TGFβ2 neutralization and TAM/GSC co-culture

    PMID:38479552

    Open questions at the time
    • TLR2/AKT/mTOR/c-MYC axis mechanistic links partly inferred
  35. 2024 Medium

    Linked TREM1 to microglial ferroptosis through the PERK arm of ER stress in diabetic cognitive impairment.

    Evidence LP17 and PERK inhibitor GSK2606414 in high-glucose BV2/HMC3 cells and HFD/STZ mice with iron and lipid peroxidation readouts

    PMID:39461708

    Open questions at the time
    • Pharmacological-only; how TREM1 activates PERK unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The endogenous physiological ligand(s) that cluster TREM-1 to initiate signaling, and the structural basis of how oligomerization is relayed through DAP12 to SYK across diverse cell types and opposing (pro-survival vs cell-death) outcomes, remain undefined.
  • No definitive endogenous agonist ligand identified
  • No atomic-resolution structure of the activated TREM-1/DAP12 oligomer
  • Determinants of context-dependent beneficial vs pathogenic outcomes unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 2 GO:0038024 cargo receptor activity 1 GO:0048018 receptor ligand activity 1
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
SMC4SYKTLR4TYROBP
Complex memberships
TLR4/LPS receptor complexTREM-1/DAP12 receptor complex

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 TREM-1 constitutively associates with DAP12, an ITAM-bearing adapter protein, which is required for induction of intracellular signaling downstream of TREM-1 in monocytes and neutrophils. DAP12 phosphorylation following TREM-1 activation leads to production of pro-inflammatory cytokines, chemokines, and reactive oxygen species, and triggers rapid degranulation and phagocytosis. Biochemical and functional assays in monocytes and neutrophils; review synthesizing prior experimental work Immunology letters High 18192027 23108097
2007 A TREM-1 ligand is expressed on human platelets. Using a recombinant TREM-1 fusion protein, specific binding of TREM-1 to platelets was demonstrated. TREM-1/ligand interaction on platelets is required for platelet-induced augmentation of PMN effector functions (provoked by LPS), but not for platelet/PMN complex formation (which depends on integrins and selectins). Recombinant TREM-1 fusion protein binding assay; functional PMN activation assays with platelet co-culture; TREM-1 blocking Blood Medium 17452516
2009 TREM-1-induced oxidative burst in human PMN requires phosphatidyl inositide 3-kinase (PI3K), phospholipase C, and p38MAPK. Protein kinase B (AKT) and ERK show characteristic phosphorylation patterns upon TREM-1 or TLR4 single or co-ligation, indicating individual activation pathways that synergize. Pharmacological inhibitors of PI3K, PLC, p38MAPK; Western blot analysis of AKT and ERK phosphorylation; oxidative burst assay in human PMN Journal of innate immunity Medium 20375613
2011 TREM-1 interacts with or is a component of the TLR4/LPS receptor complex in human neutrophils. Blocking anti-TREM-1 antibodies inhibited LPS-induced TNF-α production, and blocking TLR4 reduced the effects of TREM-1 cross-linking; co-localization of TREM-1 and TLR4 was observed. Blocking antibodies against TREM-1 and TLR4; TLR4-specific inhibitor; co-localization by immunofluorescence in human neutrophils; cytokine measurement European cytokine network Medium 21393102
2015 TREM-1 expression is upregulated in ischemic myocardium after MI. Trem-1 genetic invalidation or pharmacological inhibition (LR12 peptide) dampens myocardial inflammation, limits neutrophil recruitment and MCP-1 production, reduces classical monocyte mobilization to the heart, improves left ventricular function and survival. Soluble TREM-1 (sTREM-1) is detectable in plasma of acute MI patients. Trem-1 knockout mice; pharmacological inhibition with LR12 peptide; FDG-PET imaging; conductance catheter studies; n=20-22 per group Circulation research High 25840803
2016 Trem-1 genetic invalidation in chimeric Ldlr-/- and ApoE-/-/Trem-1-/- mice reduces atherosclerotic plaque size and inflammation, alters monocyte recruitment into lesions, and inhibits TLR4-initiated macrophage responses. TREM-1 plays a critical role in upregulation of CD36, thereby promoting inflammatory foam cell formation. Pharmacological blockade with LR12 peptide similarly reduces atherosclerosis. Bone marrow chimera mice (Trem-1-/-); ApoE-/-Trem-1-/- double KO; LR12 pharmacological blockade; histology; flow cytometry; gene expression Journal of the American College of Cardiology High 28007141
2016 TREM-1 is highly upregulated under dyslipidemic conditions on circulating and lesion-infiltrating myeloid cells. TREM-1 promotes atherosclerosis by synergizing with HFCD serum-derived factors to promote pro-inflammatory cytokine responses and foam cell formation, and by skewing monocyte differentiation and enhancing lipid accumulation. Trem1-/-/Apoe-/- mice exhibit substantially attenuated diet-induced atherogenesis. Trem1-/-/Apoe-/- double KO mice; human monocyte/macrophage culture with HFCD serum; cytokine assays; histology Nature communications High 27762264
2016 TREM1 facilitates microglial phagocytosis of amyloid-β. Knockdown of Trem1 in mouse primary microglia decreased Aβ phagocytosis; overexpression or agonistic antibody activation increased phagocytosis and reduced Aβ burden. Trem1 knockdown in APP/PSEN1 mice increased Aβ1-42 levels and total amyloid burden; selective overexpression on microglia ameliorated Aβ neuropathology and rescued spatial cognitive impairments. Trem1 knockdown and overexpression in primary mouse microglia; in vivo AAV-mediated expression in APP/PSEN1 mice; agonistic TREM1 antibody; Aβ phagocytosis assays; spatial memory tests Acta neuropathologica High 27670763
2018 TREM-1 is activated by multimerization/clustering at the cell surface. Levels of intracellular Ca2+ release, ROS, and cytokine production correlate with the degree of TREM-1 aggregation. LPS induces a two-step process in monocytes: upregulation then clustering of TREM-1; in neutrophils LPS induces rapid membrane reorganization of TREM-1. The ectodomain of TREM-1 homooligomerizes in a concentration-dependent manner. DAP12 stabilizes TREM-1 surface expression and multimerization. TREM-1 inhibitor LR12 limits TREM-1 multimerization, supporting ligand-induced, receptor-mediated dimerization. Native mass spectrometry; Ca2+ flux assays; ROS assays; cytokine ELISA; flow cytometry on primary human monocytes and neutrophils; TREM-1 ectodomain oligomerization in vitro Cellular & molecular immunology High 29568119
2018 TREM-1 promotes liver injury and fibrosis by intensifying hepatic inflammation. TREM-1 expression is limited to liver macrophages/monocytes and is upregulated on Kupffer cells in CCl4-induced chronic liver injury. TREM-1 signaling promotes pro-inflammatory cytokine production and inflammatory cell mobilization to injury sites. Reconstitution of Trem1-deficient mice with Trem1-sufficient Kupffer cells restored recruitment of inflammatory monocytes and severity of liver injury, establishing TREM-1 as a master regulator of Kupffer cell activation that activates hepatic stellate cells. Trem1 knockout mice; Kupffer cell reconstitution experiment; CCl4 chronic liver injury model; flow cytometry; histology; cytokine measurement The Journal of clinical investigation High 30137027
2018 TREM-1 inhibition restores impaired autophagy activity (macroautophagy and CMA) and reduces ER stress (UPR) in colitis. TREM-1 inhibition (pharmacological LR12 or genetic KO) increased ATG1/ULK-1, ATG13, ATG5, ATG16L1, MAP1LC3-I/II, HSPA8, HSP90AA1 and decreased PERK, IRE-1α, ATF-6α expression in colitic mice. TREM-1 inhibition also prevented dysbiosis. LR12 pharmacological inhibition; Trem-1 KO mice; DSS colitis model; Western blotting for autophagy and UPR markers; MiSeq microbiota sequencing Journal of Crohn's & colitis Medium 28961797
2019 TREM-1 interacts directly with spleen tyrosine kinase (SYK) in microglia. TREM-1 activates downstream pro-inflammatory pathways CARD9/NF-κB and NLRP3/caspase-1 through SYK interaction. TREM-1-induced SYK activation promotes microglial pyroptosis by elevating gasdermin D (GSDMD) and its N-terminal fragment (GSDMD-N), forming pores that release intracellular inflammatory factors. Co-immunoprecipitation (TREM-1/SYK interaction); Western blot for pathway components; in vivo MCAO mouse model and in vitro microglial cultures; LP17 pharmacological inhibition Cell death & disease Medium 31324751
2019 Peripheral CD11b+CD45+ myeloid TREM1 induction amplifies stroke injury via pro-inflammatory innate immune activation. Following stroke, noradrenergic-dependent increases in gut permeability induce TREM1 on Ly6C+MHCII+ intestinal lamina propria macrophages, further increasing epithelial permeability and facilitating bacterial translocation. Genetic or pharmacological TREM1 inhibition improved outcome via antioxidant and anti-inflammatory mechanisms. TREM1 genetic KO; pharmacological inhibition; PET imaging with radiolabeled anti-TREM1 antibody; trafficking studies; intestinal permeability assays in MCAO stroke model Nature immunology High 31263278
2019 TREM1 protects HIV-1-infected macrophages from apoptosis through maintenance of mitochondrial function. Upon HIV infection, TREM1 expression increases along with BCL2, BCLXL, MFN1, MFN2 and BIM translocation to mitochondria. TREM1 silencing in HIV-infected macrophages decreased BCL2, BCLXL, MFN1, MFN2, increased BAD and BAX, causing disruption of mitochondrial membrane potential (Δψm), cytochrome c release, caspase 9 cleavage, and apoptosis. HIV Tat, gp120, and TLR8 agonist RNA40 recapitulate these effects. TREM1 siRNA silencing in HIV-infected macrophages; mitochondrial membrane potential assay; cytochrome c release; Western blot for BCL2 family proteins; apoptosis assays mBio High 31719184
2019 TREM-1 regulates neutrophil chemotaxis by promoting NOX2-dependent superoxide production. Trem1-deficient peritoneal neutrophils show impaired NOX2-dependent superoxide production (measured by EPR spectroscopy) and reduced oxygen consumption. TREM-1-deficient neutrophils have impaired directional migration toward fMLP and zymosan-activated serum. TREM-1 regulates neutrophil migratory properties in part by promoting AKT activation and NOX2-dependent superoxide production. Trem1 knockout mice; electron paramagnetic resonance spectroscopy for superoxide; Clark electrode for oxygen consumption; directional migration assay; AKT phosphorylation by Western blot Journal of leukocyte biology High 30667543
2020 TREM-1 triggers microglial pyroptosis via activating NLRP3 inflammasome following subarachnoid hemorrhage. Recombinant TREM-1 (mimic) worsened outcomes, while LP17 antagonist ameliorated pyroptosis by diminishing GSDMD-N and IL-1β production in microglia. Mechanistically confirmed both in vivo (SAH mouse model) and in vitro. Intranasal LP17 administration; recombinant TREM-1 administration; SAH mouse model; Western blot for NLRP3, caspase-1, GSDMD, GSDMD-N, IL-1β; in vitro microglial cultures Translational stroke research Medium 32862402
2020 Extracellular CIRP (eCIRP) activates TREM-1 on neutrophils, which generates ICAM-1+ neutrophils. ICAM-1+ neutrophils then promote NET formation via Rho GTPase activation. TREM-1-/- neutrophils or LP17-pretreated neutrophils showed significantly decreased ICAM-1 expression after rmCIRP treatment. Blockade of ICAM-1 significantly decreased Rho activation and NET formation. TREM-1-/- mice; LP17 pharmacological inhibition; rmCIRP injection; flow cytometry; Rho activation assay; NET quantification; ICAM-1 blocking antibody FASEB journal Medium 32506691
2020 TREM-1 activation in macrophages induces endoplasmic reticulum stress through the IRE-1α/XBP-1s pathway. Agonistic anti-TREM-1 antibody increased expression of ER stress markers (ATF6, PERK, IRE-1α, XBP-1s) and pro-inflammatory cytokines. Inhibiting IRE-1α/XBP-1s with STF-083010 or XBP-1 silencing attenuated TREM-1-induced cytokine production. TREM-1 blockade (LR12) ameliorated ER stress in vitro and in vivo. Agonistic anti-TREM-1 antibody; STF-083010 IRE-1α inhibitor; XBP-1 siRNA silencing; 4-PBA ER stress inhibitor; Western blot; primary macrophage cultures; LPS-induced ALI mouse model Molecular immunology Medium 33957479
2020 Tryptophanyl-tRNA synthetase 1 (WARS1) activates TREM-1 expression at both mRNA and protein levels via TLR2 and TLR4, mediated by both MyD88 and TRIF. Targeted deletion of TLR4, TLR2, MyD88, and TRIF abrogated TREM-1 activation. WARS1 promoted TREM-1 downstream phosphorylation of DAP12, Syk, and AKT. Knockdown of TREM-1 or inhibition of Syk suppressed the inflammatory signaling loop (p38 MAPK, ERK, NF-κB), reducing cytokine production. TLR4/TLR2/MyD88/TRIF knockout cells; TREM-1 knockdown; Syk kinase inhibitor; Western blot for DAP12, Syk, AKT phosphorylation; cytokine ELISA Biomolecules Medium 32899943
2021 TREM-1 orchestrates angiotensin II-induced monocyte trafficking and promotes abdominal aortic aneurysm. TREM-1 on Ly6Chi monocytes is activated by AngII via AT1R signaling. Antibody-mediated TREM-1 stimulation exacerbated Ly6Chi monocyte aorta infiltration via CD62L upregulation. Trem1 gene deletion attenuated aortic inflammation (reduced Il1b, Tnfa, Mmp2, Mmp9 mRNA) and macrophage content. Apoe-/-Trem1-/- mice; AngII-induced AAA model; LR12 pharmacological blockade; anti-TREM-1 stimulating antibody; flow cytometry; qRT-PCR The Journal of clinical investigation High 33258804
2021 TREM-1 regulates macrophage M1 polarization via the STAT3/HIF-1α signaling pathway. Knockdown of Trem1 in RAW 264.7 cells decreased M1 polarization and increased M2 polarization; overexpression had the opposite effect. Trem1 knockout mice showed limited macrophage infiltration and decreased M1 gene expression in periodontitis lesions. Trem1 siRNA knockdown and overexpression in RAW 264.7 macrophages; Trem1 KO mice; flow cytometry; Western blotting; RT-qPCR; RNA sequencing identifying STAT3/HIF-1α pathway Journal of dental research Medium 34719965
2021 TREM-1 cooperates with diminished DNA damage response to promote pre-leukemia stem cell (pre-LSC) expansion in Fanconi anemia. shRNA knockdown of Trem1 in Fanca-/- pre-LSCs improved leukemia-related survival but did not affect DDR or genomic instability, placing TREM-1 downstream or parallel to DDR in leukemogenic transformation. Trem1 shRNA knockdown; Fanca-/- mouse model; in vivo transplantation; survival analysis; gene expression profiling Leukemia Medium 27568523
2022 TREM-1 induces cardiomyocyte pyroptosis via NLRP3 inflammasome activation through the SMC4/NEMO pathway in sepsis. TREM-1 and SMC4 were found to interact closely. Inhibition of TREM-1 or SMC4 prevented NLRP3 upregulation and decreased Gasdermin-D, IL-1β and caspase-1 cleavage in HL-1 cardiomyocytes. LR12 in CLP mice decreased NLRP3 expression and attenuated pyroptosis, improving cardiac function and survival. Co-immunoprecipitation (TREM-1/SMC4 interaction); siRNA inhibition of TREM-1 and SMC4; LPS/nigericin-stimulated HL-1 cells; CLP sepsis mouse model; LR12 peptide; Western blot The FEBS journal Medium 36181338
2022 TREM-1 exacerbates pulmonary fibrosis by promoting alveolar epithelial cell (AEC) senescence. TREM-1 was upregulated in AECs (not just macrophages) in bleomycin-treated mice and correlated with senescence markers. Agonistic TREM-1 antibody exacerbated BLM-induced senescence in MLE12 cells; blockade with LR12 reduced p16, p21, p53, γ-H2AX expression and attenuated fibrosis. LR12 prophylactic and therapeutic blockade; agonistic TREM-1 antibody in MLE12 cells; BLM-induced PF mouse model; Western blot for senescence markers; histology International immunopharmacology Medium 36330909
2022 TREM-1 activation in macrophages promotes NLRP3 inflammasome activation through metabolic reprogramming: TREM-1 activation enhances glycolysis and inhibits oxidative phosphorylation via the PI3K/AKT/mTOR pathway, leading to HIF-1α accumulation and nuclear translocation, which drives glycolysis-dependent NLRP3/caspase-1 activation. Inhibiting mTOR, HIF-1α, or glycolysis (2-DG) suppressed TREM-1-induced NLRP3 activation. TREM-1 agonist antibody; 2-deoxyglucose glycolysis inhibition; mTOR inhibitor rapamycin; HIF-1α inhibitor; glucose consumption assay; Western blot; LPS-induced ALI mouse model; LR12 blockade International journal of biological sciences Medium 36594089
2022 Endothelial TREM-1 signals via SYK/β-catenin pathway to regulate blood-brain barrier integrity after intracerebral hemorrhage. TREM-1 activation reduces β-catenin, claudin-5, and ZO-1 expression. SYK activation CRISPR abolished the beneficial effect of TREM-1 blockade on junction molecules; the SYK inhibitor R406 reversed the impact of TREM-1 agonist on β-catenin, claudin-5, and ZO-1 downregulation. LP17 intranasal administration; SYK activation CRISPR intracerebroventricularly; anti-TREM-1 agonist IgG; SYK inhibitor R406; ICH collagenase mouse model; Western blot; BBB permeability assay CNS neuroscience & therapeutics Medium 37170484
2022 eCIRP activates TREM-1 on renal endothelial cells to induce AKI. TREM-1-/- mice had attenuated AKI and reduced ICAM-1 expression in renal tissue after rmCIRP injection. TREM-1 inhibitory peptide M3 attenuated human renal glomerular endothelial cell activation (cytokine production and sTREM-1 release) after eCIRP stimulation. TREM-1-/- mice; rmCIRP injection; M3 inhibitory peptide; primary human renal glomerular endothelial cell culture; serum BUN/creatinine/NGAL measurement; mRNA and protein expression Frontiers in physiology Medium 36246143
2023 TREM-1 triggers macrophage necroptosis through mTOR-dependent mitochondrial fission during ALI. TREM-1 activation (agonist anti-TREM-1 Ab) induced necroptosis in macrophages. mTOR signaling promotes TREM-1-mediated DRP1Ser616 phosphorylation, causing surplus mitochondrial fission leading to necroptosis. Inhibiting mTOR (rapamycin), DRP1 (Mdivi-1), or RIPK3 (GSK872) all reduced TREM-1-triggered necroptosis. Agonist anti-TREM-1 antibody; RIPK3 inhibitor GSK872; DRP1 inhibitor Mdivi-1; mTOR inhibitor rapamycin; LR12 in LPS-induced ALI mice; Western blot for DRP1Ser616 phosphorylation; necroptosis assays Journal of translational medicine Medium 36879273
2023 Accumulated lipid droplets (LDs) in microglia co-localize with TREM1, resulting in TREM1 buildup. TREM1 accumulation in turn aggravates HG-induced lipophagy damage and promotes neuroinflammatory cascades via NLRP3 inflammasome. LP17 blockade of TREM1 inhibited LD and TREM1 accumulation and reduced hippocampal neuronal inflammatory damage. Co-immunoprecipitation (LDs/TREM1 co-localization); db/db and HFD/STZ mouse models; LP17 pharmacological blockade; HG-treated BV2, HMC3 and primary microglia; Western blot; immunofluorescence; behavioral tests Autophagy Medium 37204119
2023 TREM1 promotes gastric cancer progression through NETs-mediated M2 macrophage polarization. TREM1 deficiency hindered tumor growth, reduced neutrophil infiltration, reduced NETs formation, and stimulated M1 (rather than M2) macrophage polarization. DNase-1 (NETs degrader) counteracted the impacts of TREM1 on GC, placing TREM1 upstream of NETs in this pathway. TREM1 KO and knock-in GC mice; MNNG-induced GC model; DNase-1 treatment; flow cytometry for macrophage polarization; immunofluorescence and Western blot for NETs markers; IHC Digestive and liver disease Medium 38151453
2023 TREM1 in microglia is upregulated by HIV Tat through a TLR4/TICAM1/COX-2/PGE synthase/PGE2-dependent pathway. TREM1 silencing in HIV-infected microglia induces cell death without increased viral or pro-inflammatory cytokine expression. TREM1 siRNA silencing in HIV-infected human microglia; TLR4 blocking; COX-2 and PGE2 pathway inhibitors; apoptosis assays; cytokine measurement Journal of immunology Medium 37326481
2024 Trem1 deficiency prevents age-dependent changes in myeloid metabolism and inflammation. Trem1-deficient microglia are resistant to amyloid-β42 oligomer-induced bioenergetic changes in vitro. Trem1 haploinsufficiency in 5XFAD mice prevents spatial memory loss, preserves homeostatic microglial morphology, reduces neuritic dystrophy and disease-associated microglial transcriptomic signature changes. In aging APPSwe mice, Trem1 deficiency prevents hippocampal memory decline while restoring synaptic mitochondrial function and cerebral glucose uptake. TREM1 colocalizes with Iba1+ cells around amyloid plaques in postmortem AD brain. Trem1 KO and haploinsufficiency in 5XFAD and APPSwe mouse models; metabolomics (ribose 5-phosphate); in vitro bioenergetics assay; spatial memory testing; microglial morphology analysis; transcriptomics; PET imaging for glucose uptake; postmortem AD brain immunohistochemistry Nature neuroscience High 38539014
2024 TREM1 modulates M1 macrophage polarization via STAT3/HIF-1α axis. In microglia, TREM1 regulates NLRP3 activation via the NF-κB pathway: TREM1 overexpression activates NF-κB, upregulates NLRP3 components and pro-inflammatory cytokines; NF-κB inhibitor PDTC reversed this. TREM1 knockdown attenuated LPS-induced NF-κB pathway activation. TREM1 siRNA knockdown; TREM1 overexpression plasmid; NF-κB inhibitor PDTC; LPS-treated BV2 cells; Western blotting; immunofluorescence; NTG-induced chronic migraine mouse model; LR12 inhibition The journal of headache and pain Medium 38177990
2024 TREM1 aggravates microglial ferroptosis through the PERK pathway of endoplasmic reticulum stress in diabetes-associated cognitive impairment. High glucose activates the PERK-ERS pathway; TREM1 inhibition with LP17 or PERK inhibitor GSK2606414 reversed ferroptosis (iron accumulation, GSH/GSSG reduction, lipid peroxidation, ROS) in BV2/HMC3 microglia and in vivo. LP17 pharmacological blockade; PERK inhibitor GSK2606414; HG-treated BV2 and HMC3 cells; HFD/STZ mouse model; Prussian blue staining for iron; Western blot; transmission electron microscopy; Y-maze and NOR behavioral tests Experimental neurology Medium 39461708
2024 In glioblastoma, hypoxia-induced TREM1 in M2-like TAMs promotes mesenchymal-like states of glioma stem cells by modulating TGFβ2 secretion, which activates TGFβR/SMAD2/3 signaling in GSCs. TREM1 expression in TAMs is transcriptionally regulated by HIF-1α under hypoxic conditions and promotes immunosuppressive TAM polarization via the TLR2/AKT/mTOR/c-MYC axis. HIF-1α ChIP; TREM1 overexpression and knockdown in TAMs; TGFβ2 neutralization; SMAD2/3 Western blot; co-culture of TAMs and GSCs; TLR2/AKT/mTOR pathway inhibitors Cancer letters Medium 38479552
2010 TREM-1 expression in macrophages in response to LPS and Pseudomonas aeruginosa is inhibited by prostaglandins PGD2, PGJ2, and 15-dPGJ2. This inhibition is independent of PGD2 receptors and PPARγ, but occurs through activation of Nrf2 and inhibition of NF-κB. Macrophage cell line treated with prostaglandins; PGD2 receptor antagonists; PPARγ antagonist/agonist; Nrf2 activation assay; NF-κB inhibition assay; TREM-1 expression by Western blot and flow cytometry Experimental cell research Medium 20797396
2013 TREM-1 is crucial for macrophage polarization toward M1 phenotype. Kidney lysates from nephritic kidneys triggered TREM-1-dependent M1 polarization ex vivo. GM-CSF-derived M1 macrophages express higher levels of TREM-1 than M-CSF-derived cells. TREM-1 cross-linking strengthens induction of iNOS and GM-CSF in M1 macrophages. Ex vivo macrophage stimulation with nephritic kidney lysates; Trem-1 blocking antibody; ureteral obstruction mouse model; TREM-1 agonistic cross-linking; Western blot; flow cytometry; histology Kidney international Medium 24918157
2019 Rheumatoid arthritis synovial fibroblasts (RASF) promote TREM-1 expression in CD14+ monocytes via COX-2/PGE2/EP2,4 signaling. Soluble factors (not direct cell contact) mediate this effect, as shown by transwell assay. COX-2 inhibitors, COX-2 siRNA, and EP1-4 antagonists each abrogated RASF-promoted TREM-1 upregulation in monocytes. RASF-monocyte co-culture; transwell assay; COX-2 siRNA; COX-2 inhibitors; EP1-4 antagonists; PGE2 ELISA; TREM-1 flow cytometry Arthritis research & therapy Medium 31287012
2019 TREM-1 activation alleviates hyperoxia-induced lung injury in neonatal mice through downregulating RIPK3-mediated necroptosis and NLRP3 inflammasome activation. TREM-1 siRNA or Trem1 gene deletion enhanced lung inflammation and mortality under hyperoxia. Agonistic TREM-1 antibody treatment decreased lung inflammation, improved alveolarization, and diminished RIPK3 expression. Trem1 siRNA; Trem1 KO mice; agonistic TREM-1 antibody; neonatal hyperoxia model; Western blot for RIPK3, NLRP3; histology; survival analysis American journal of respiratory cell and molecular biology Medium 30281332
2016 LXR, RXR, RAR, and VDR nuclear receptor ligands induce TREM-1 expression on dendritic cells. TREM-1 triggering induced by retinoids increased TNFα and IL-1β release, establishing an active inflammatory role for NRL-activated TREM-1+ DCs. Transcriptomic profiling of DCs treated with 22R-HC; TREM-1 protein expression assay; cytokine ELISA after TREM-1 triggering; RXR/RAR/VDR ligand treatment; Trem-1 bone marrow chimera mouse tumor model Oncoimmunology Medium 30723587
2023 TREM1 agonism via afucosylated humanized anti-TREM1 antibody (PY159, with enhanced FcγR binding) induces TREM1 signaling leading to upregulation of costimulatory molecules on monocytes/macrophages, production of pro-inflammatory cytokines and chemokines, and enhancement of T cell activation in vitro. Anti-mouse TREM1 antibody PY159m promoted antitumor efficacy in syngeneic tumor models. Anti-TREM1 agonist antibody (PY159); cytokine/chemokine measurement; costimulatory molecule expression by flow cytometry; T cell activation assay; syngeneic mouse tumor models Science translational medicine Medium 37647386
2016 LPS induces TREM-1-dependent HIF-1α expression in human HaCaT keratinocytes via the PI3K/Akt pathway. TREM-1 siRNA silencing suppressed LPS-induced PI3K/Akt phosphorylation and HIF-1α expression. PI3K inhibitor wortmannin blocked HIF-1α induction without affecting TREM-1 expression itself, placing TREM-1 upstream of PI3K/Akt/HIF-1α. TREM-1 siRNA; PI3K inhibitor wortmannin; LPS-stimulated HaCaT keratinocytes; Western blot for pAkt, HIF-1α, TREM-1; immunofluorescence Cell biology international Low 27743451

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Microglial TREM-1 receptor mediates neuroinflammatory injury via interaction with SYK in experimental ischemic stroke. Cell death & disease 219 31324751
2017 TREM-1 and its potential ligands in non-infectious diseases: from biology to clinical perspectives. Pharmacology & therapeutics 202 28245991
2012 TREM-1: intracellular signaling pathways and interaction with pattern recognition receptors. Journal of leukocyte biology 189 23108097
2020 TREM-1 Exacerbates Neuroinflammatory Injury via NLRP3 Inflammasome-Mediated Pyroptosis in Experimental Subarachnoid Hemorrhage. Translational stroke research 178 32862402
2008 From expression to signaling: roles of TREM-1 and TREM-2 in innate immunity and bacterial infection. Immunobiology 174 18926286
2007 TREM-1 ligand expression on platelets enhances neutrophil activation. Blood 174 17452516
2023 Impaired lipophagy induced-microglial lipid droplets accumulation contributes to the buildup of TREM1 in diabetes-associated cognitive impairment. Autophagy 169 37204119
2007 The TREM-1/DAP12 pathway. Immunology letters 169 18192027
2019 Low TREM1 expression in whole blood predicts anti-TNF response in inflammatory bowel disease. EBioMedicine 138 30685385
2019 Peripheral TREM1 responses to brain and intestinal immunogens amplify stroke severity. Nature immunology 138 31263278
2023 TREM-1 governs NLRP3 inflammasome activation of macrophages by firing up glycolysis in acute lung injury. International journal of biological sciences 131 36594089
2007 TREM-1 expression in tumor-associated macrophages and clinical outcome in lung cancer. American journal of respiratory and critical care medicine 123 18096709
2015 TREM-1 Mediates Inflammatory Injury and Cardiac Remodeling Following Myocardial Infarction. Circulation research 118 25840803
2020 Androgen receptor signalling in macrophages promotes TREM-1-mediated prostate cancer cell line migration and invasion. Nature communications 97 32908142
2014 Triggering receptor expressed on myeloid cells-1 (TREM-1): a new player in antiviral immunity? Frontiers in microbiology 96 25505454
2016 Genetic and Pharmacological Inhibition of TREM-1 Limits the Development of Experimental Atherosclerosis. Journal of the American College of Cardiology 91 28007141
2016 TREM-1 links dyslipidemia to inflammation and lipid deposition in atherosclerosis. Nature communications 88 27762264
2022 Single-cell RNA sequencing identifies an Il1rn+/Trem1+ macrophage subpopulation as a cellular target for mitigating the progression of thoracic aortic aneurysm and dissection. Cell discovery 86 35132073
2018 The innate immune receptor TREM-1 promotes liver injury and fibrosis. The Journal of clinical investigation 83 30137027
2018 TREM-1 multimerization is essential for its activation on monocytes and neutrophils. Cellular & molecular immunology 81 29568119
2016 TREM1 facilitates microglial phagocytosis of amyloid beta. Acta neuropathologica 76 27670763
2021 TREM-1 orchestrates angiotensin II-induced monocyte trafficking and promotes experimental abdominal aortic aneurysm. The Journal of clinical investigation 74 33258804
2018 TREM-1 Inhibition Restores Impaired Autophagy Activity and Reduces Colitis in Mice. Journal of Crohn's & colitis 71 28961797
2024 Microglia TREM1-mediated neuroinflammation contributes to central sensitization via the NF-κB pathway in a chronic migraine model. The journal of headache and pain 63 38177990
2023 Prospective evaluation of the efficacy, safety, and optimal biomarker enrichment strategy for nangibotide, a TREM-1 inhibitor, in patients with septic shock (ASTONISH): a double-blind, randomised, controlled, phase 2b trial. The Lancet. Respiratory medicine 60 37269870
2020 Function of TREM1 and TREM2 in Liver-Related Diseases. Cells 60 33297569
2011 TREM-1 interaction with the LPS/TLR4 receptor complex. European cytokine network 58 21393102
2022 TREM-1 Modulation Strategies for Sepsis. Frontiers in immunology 57 35784361
2020 Extracellular CIRP and TREM-1 axis promotes ICAM-1-Rho-mediated NETosis in sepsis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 57 32506691
2019 TREM-1 Protects HIV-1-Infected Macrophages from Apoptosis through Maintenance of Mitochondrial Function. mBio 56 31719184
2014 TREM-1 regulates macrophage polarization in ureteral obstruction. Kidney international 55 24918157
2023 TREM-1 triggers necroptosis of macrophages through mTOR-dependent mitochondrial fission during acute lung injury. Journal of translational medicine 54 36879273
2020 TREM-1-targeting LP17 attenuates cerebral ischemia-induced neuronal injury by inhibiting oxidative stress and pyroptosis. Biochemical and biophysical research communications 48 32736673
2024 TREM1: Activation, signaling, cancer and therapy. Pharmacological research 47 38749377
2017 TREM-1 promotes intestinal tumorigenesis. Scientific reports 46 29093489
2022 The associations between plasma soluble Trem1 and neurological diseases: a Mendelian randomization study. Journal of neuroinflammation 44 36068612
2024 TREM1 disrupts myeloid bioenergetics and cognitive function in aging and Alzheimer disease mouse models. Nature neuroscience 43 38539014
2021 TREM-1 promoted apoptosis and inhibited autophagy in LPS-treated HK-2 cells through the NF-κB pathway. International journal of medical sciences 43 33390769
2013 TREM-1 inhibition attenuates inflammation and tumor within the colon. International immunopharmacology 42 23810411
2023 TREM1 activation of myeloid cells promotes antitumor immunity. Science translational medicine 41 37647386
2022 FOXM1 network in association with TREM1 suppression regulates NET formation in diabetic foot ulcers. EMBO reports 41 35856334
2016 Therapeutic Potential of Targeting TREM-1 in Inflammatory Diseases and Cancer. Current pharmaceutical design 41 27568730
2019 Therapeutic Effect of Modulating TREM-1 via Anti-inflammation and Autophagy in Parkinson's Disease. Frontiers in neuroscience 40 31440123
2022 The role of triggering receptor expressed on myeloid cells-1 (TREM-1) in central nervous system diseases. Molecular brain 39 36273145
2004 Expression of TREM-1 mRNA in acute pancreatitis. World journal of gastroenterology 39 15309732
2017 Novel TREM-1 Inhibitors Attenuate Tumor Growth and Prolong Survival in Experimental Pancreatic Cancer. Molecular pharmaceutics 38 29095622
2009 Signaling pathways of the TREM-1- and TLR4-mediated neutrophil oxidative burst. Journal of innate immunity 38 20375613
2020 The role of the triggering receptor expressed on myeloid cells-1 (TREM-1) in non-bacterial infections. Critical reviews in microbiology 35 32326783
2022 Tumor-Infiltrating Myeloid Cells Co-Express TREM1 and TREM2 and Elevated TREM-1 Associates With Disease Progression in Renal Cell Carcinoma. Frontiers in oncology 34 35223446
2020 Tryptophanyl-tRNA Synthetase 1 Signals Activate TREM-1 via TLR2 and TLR4. Biomolecules 34 32899943
2018 Soluble TREM-1 as a predictive factor of neonatal sepsis: a meta-analysis. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 34 29644420
2021 Trem1 Induces Periodontal Inflammation via Regulating M1 Polarization. Journal of dental research 33 34719965
2020 Triggering receptor expressed on myeloid cells-1 (TREM-1) as a therapeutic target in infectious and noninfectious disease: a critical review. International reviews of immunology 33 32379561
2019 TREM-1 regulates neutrophil chemotaxis by promoting NOX-dependent superoxide production. Journal of leukocyte biology 32 30667543
2019 Regulation of PGLYRP1 and TREM-1 during Progression and Resolution of Gingival Inflammation. JDR clinical and translational research 32 31013451
2010 Expression of TREM-1 is inhibited by PGD2 and PGJ2 in macrophages. Experimental cell research 32 20797396
2013 Regulation of TREM-1 expression by 1,25-dihydroxyvitamin D3 in human monocytes/macrophages. Immunology letters 30 24012964
2016 GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis. Molecular medicine (Cambridge, Mass.) 29 26650186
2019 Rheumatoid arthritis synovial fibroblasts promote TREM-1 expression in monocytes via COX-2/PGE2 pathway. Arthritis research & therapy 28 31287012
2021 TREM-1+ Macrophages Define a Pathogenic Cell Subset in the Intestine of Crohn's Disease Patients. Journal of Crohn's & colitis 27 33537747
2018 TREM1 mRNA Expression in Leukocytes and Cognitive Function in Japanese Patients with Alzheimer's Disease. Journal of Alzheimer's disease : JAD 26 30010135
2018 TREM-1; Is It a Pivotal Target for Cardiovascular Diseases? Journal of cardiovascular development and disease 26 30205488
2023 Acteoside alleviates UUO-induced inflammation and fibrosis by regulating the HMGN1/TLR4/TREM1 signaling pathway. PeerJ 25 36691481
2021 Elevated serum TREM-1 is associated with periodontitis and disease activity in rheumatoid arthritis. Scientific reports 25 33536478
2022 Triggering receptor expressed on myeloid cells-1 (TREM-1) inhibition in atherosclerosis. Pharmacology & therapeutics 24 35390422
2019 TREM-1 Attenuates RIPK3-mediated Necroptosis in Hyperoxia-induced Lung Injury in Neonatal Mice. American journal of respiratory cell and molecular biology 24 30281332
2018 Genes interconnecting AMPK and TREM-1 and associated microRNAs in rotator cuff tendon injury. Molecular and cellular biochemistry 24 30306456
2020 TREM-1 and TREM-2 Expression on Blood Monocytes Could Help Predict Survival in High-Grade Glioma Patients. Mediators of inflammation 23 32684831
2023 TREM1 facilitates the development of gastric cancer through regulating neutrophil extracellular traps-mediated macrophage polarization. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 22 38151453
2018 Idelalisib impairs TREM-1 mediated neutrophil inflammatory responses. Scientific reports 22 29615799
2022 TREM1 fosters an immunosuppressive tumor microenvironment in papillary thyroid cancer. Endocrine-related cancer 21 34860175
2022 Inhibition of the Interaction of TREM-1 and eCIRP Attenuates Inflammation and Improves Survival in Hepatic Ischemia/Reperfusion. Shock (Augusta, Ga.) 20 34864782
2022 TREM-1 induces pyroptosis in cardiomyocytes by activating NLRP3 inflammasome through the SMC4/NEMO pathway. The FEBS journal 20 36181338
2022 Extracellular CIRP induces acute kidney injury via endothelial TREM-1. Frontiers in physiology 20 36246143
2022 TREM-1 exacerbates bleomycin-induced pulmonary fibrosis by aggravating alveolar epithelial cell senescence in mice. International immunopharmacology 20 36330909
2019 Inhibition of TREM-1 attenuates inflammation and lipid accumulation in diet-induced nonalcoholic fatty liver disease. Journal of cellular biochemistry 20 30805986
2019 TREM1/Dap12-based CAR-T cells show potent antitumor activity. Immunotherapy 20 31268375
2012 TREM-1 Promotes Pancreatitis-Associated Intestinal Barrier Dysfunction. Gastroenterology research and practice 20 22611379
2022 Circular RNA hsa_circ_0083756 promotes intervertebral disc degeneration by sponging miR-558 and regulating TREM1 expression. Cell proliferation 19 35187741
2024 Osteoclast-derived exosomes influence osteoblast differentiation in osteoporosis progression via the lncRNA AW011738/ miR-24-2-5p/ TREM1 axis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 18 39094542
2023 Endothelial TREM-1 receptor regulates the blood-brain barrier integrity after intracerebral hemorrhage in mice via SYK/β-catenin signaling. CNS neuroscience & therapeutics 18 37170484
2022 A novel eCIRP/TREM-1 pathway inhibitor attenuates acute kidney injury. Surgery 18 35292178
2019 TREM-1 deficiency attenuates the inflammatory responses in LPS-induced murine endometritis. Microbial biotechnology 18 31365951
2024 Hypoxia-induced TREM1 promotes mesenchymal-like states of glioma stem cells via alternatively activating tumor-associated macrophages. Cancer letters 17 38479552
2023 The orchestrating role of deteriorating neurons and TREM-1 in crosstalk with SYK in Alzheimer's disease progression and neuroinflammation. Inflammopharmacology 16 37405587
2021 TREM-1 isoforms in bacterial infections: to immune modulation and beyond. Critical reviews in microbiology 16 33522328
2018 Nuclear receptor ligands induce TREM-1 expression on dendritic cells: analysis of their role in tumors. Oncoimmunology 16 30723587
2016 Data on TREM-1 activation destabilizing carotid plaques. Data in brief 16 27331093
2016 The immune receptor Trem1 cooperates with diminished DNA damage response to induce preleukemic stem cell expansion. Leukemia 16 27568523
2016 Lipopolysaccharide induces TREM-1-dependent HIF-1α expression in human keratinocyte cell line. Cell biology international 16 27743451
2024 Inhibition of TREM-1 alleviates neuroinflammation by modulating microglial polarization via SYK/p38MAPK signaling pathway after traumatic brain injury. Brain research 15 38570153
2024 TREM1 induces microglial ferroptosis through the PERK pathway in diabetic-associated cognitive impairment. Experimental neurology 15 39461708
2023 Jo-1 Antibodies From Myositis Induce Complement-Dependent Cytotoxicity and TREM-1 Upregulation in Muscle Endothelial Cells. Neurology(R) neuroimmunology & neuroinflammation 15 37147138
2021 Activation of TREM-1 induces endoplasmic reticulum stress through IRE-1α/XBP-1s pathway in murine macrophages. Molecular immunology 15 33957479
2024 TREM1/DAP12 based novel multiple chain CAR-T cells targeting DLL3 show robust anti-tumour efficacy for small cell lung cancer. Immunology 14 38469682
2024 Inhibition of TREM-1 ameliorates angiotensin II-induced atrial fibrillation by attenuating macrophage infiltration and inflammation through the PI3K/AKT/FoxO3a signaling pathway. Cellular signalling 14 39384003
2023 HIV-1 Tat Upregulates TREM1 Expression in Human Microglia. Journal of immunology (Baltimore, Md. : 1950) 14 37326481
2023 TREM-1, TREM-2 and their association with disease severity in patients with COVID-19. Annals of medicine 14 37848000
2022 TREM-1 Modulates Dendritic Cells Maturation and Dendritic Cell-Mediated T-Cell Activation Induced by ox-LDL. Oxidative medicine and cellular longevity 14 35637975
2021 Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) Contributes to Bordetella pertussis Inflammatory Pathology. Infection and immunity 14 34097504

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