TREM2 inhibition triggers antitumor cell activity of myeloid cells in glioblastoma

Science Advances, Год журнала: 2023, Номер 9(19)

Опубликована: Май 12, 2023

Triggering receptor expressed on myeloid cells 2 (TREM2) plays important roles in brain microglial function neurodegenerative diseases, but the role of TREM2 GBM TME has not been examined. Here, we found that is highly subsets, including macrophages and microglia human mouse tumors high expression correlates with poor prognosis patients GBM. loss increased interferon-γ–induced immunoactivation, proinflammatory polarization, tumoricidal capacity. In orthotopic models, mice chronic acute Trem2 exhibited decreased tumor growth survival. inhibition reprogrammed phenotypes programmed cell death protein 1 (PD-1) + CD8 T TME. Last, deficiency enhanced effectiveness anti–PD-1 treatment, which may represent a therapeutic strategy for

Язык: Английский

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TREM2: Potential therapeutic targeting of microglia for Alzheimer's disease

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 165, С. 115218 - 115218

Опубликована: Июль 29, 2023

Alzheimer's disease (AD) is the most common neurodegenerative disease, resulting in loss of cognitive ability and memory. However, there no specific treatment to mechanistically inhibit progression drugs only provide symptom relief do not fundamentally reverse AD. Current studies show that triggering receptor expressed on myeloid cells 2 (TREM2) predominantly microglia central nervous system (CNS) involved proliferation, survival, migration phagocytosis. The current academic view suggests TREM2 its ligands have CNS protective effects Specifically, acts by regulating function promoting clearance neuronal toxic substances abnormal proteins microglia. In addition, also inflammatory response cell signaling pathways, affecting immune regulatory role Although relationship between has been extensively studied, mechanism action fully understood. purpose this review a comprehensive analysis research TREM2, including regulation response, lipid metabolism phagocytosis AD, explore potential application prospects as well limitations targeting for

Язык: Английский

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TREM2 promotes macrophage polarization from M1 to M2 and suppresses osteoarthritis through the NF-κB/CXCL3 axis

International Journal of Biological Sciences, Год журнала: 2024, Номер 20(6), С. 1992 - 2007

Опубликована: Янв. 1, 2024

Objective: Osteoarthritis (OA) is the most prominent chronic arthritic disease, affecting over 3 billion people globally.Synovial macrophages, as immune cells, play an essential role in cartilage damage OA.Therefore, regulating macrophages crucial for controlling pathological changes OA.Triggering receptor expressed on myeloid cells 2 (TREM2), cell surfaces, such and dendritic has suppressed inflammation regulated M2 macrophage polarization but demonstrated unknown synovial OA.This study aimed to investigate TREM2 expression downregulation OA mice macrophages.Furthermore, trend of was associated with polarization-related molecule mice.Results: We used knockout (TREM2-KO) observe that deficiency significantly exacerbated joint response mice, thereby accelerating disease progression.Separating chondrocytes from TREM2-KO co-cultivating them increased chondrocyte apoptosis inhibited proliferation.Further, also enhanced phosphatidylinositol 3-kinase(PI3K)/AKT signaling pathway activation, increasing nuclear factor kappa light chain enhancer activated B (NF-κB) C-X-C Motif Chemokine Ligand (CXCL3) expression.Furthermore, NF-κB inhibition arthritis effectively alleviating deficiency-related adverse effects chondrocytes.Notably, knocking down CXCL3 inhibits inflammatory promotes proliferation.Intravenous recombinant protein (soluble TREM2, sTREM2) injection markedly M1 improves tissue pathology OA.Conclusion: Our reveals during by NF-κB/CXCL3 axis regulation, improving state OA.

Язык: Английский

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Functional diversity of cardiac macrophages in health and disease

Nature Reviews Cardiology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Язык: Английский

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TREM2 regulates microglial lipid droplet formation and represses post-ischemic brain injury

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 170, С. 115962 - 115962

Опубликована: Дек. 1, 2023

Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein predominantly in microglia within the central nervous system (CNS). TREM2 regulates multiple microglial functions, including lipid metabolism, immune reaction, inflammation, and phagocytosis. Recent studies have found that highly activated after ischemic stroke. However, role of pathologic response stroke remains unclear. Herein, TREM2-deficient exhibit an impaired phagocytosis rate cholesteryl ester (CE) accumulation, leading to droplet formation upregulation Perilipin-2 (PLIN2) expression hypoxia. Knockdown results increased synthesis (PLIN2, SOAT1) decreased cholesterol clearance hydrolysis (LIPA, ApoE, ABCA1, NECH1, NPC2), further impacting phenotypes. In these droplet-rich microglia, TGF-β1/Smad2/3 signaling pathway downregulated, driving towards pro-inflammatory phenotype. Meanwhile, neuron-microglia co-culture under hypoxic conditions, we lost their protective effect against neuronal injury apoptosis when was knocked down. Under vivo knockdown mice express lower TGF-β1 levels number anti-inflammatory M2 phenotype resulting cerebral infarct size, exacerbated apoptosis, aggravated impairment. Our work suggests attenuates stroke-induced neuroinflammation by modulating pathway. may play direct regulation inflammation also exert influence post-ischemic pathology progression via metabolism processes. Thus, underscoring therapeutic potential agonists making attractive new clinical target for treatment other inflammation-related diseases.

Язык: Английский

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Amyloid Precursor Protein and Alzheimer’s Disease

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(19), С. 14794 - 14794

Опубликована: Сен. 30, 2023

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders associated with age or inherited mutations. It characterized by severe dementia in late stages that affect memory, cognitive functions, and daily life overall. AD progression linked to accumulation cytotoxic amyloid beta (Aβ) hyperphosphorylated tau protein combined other pathological features such as synaptic loss, defective energy metabolism, imbalances protein, metal homeostasis. Several treatment options for are under investigation, including antibody-based therapy stem cell transplantation. Amyloid precursor (APP) a membrane considered play main role pathology. known APP physiological conditions follows non-amyloidogenic pathway; however, it can proceed an amyloidogenic scenario, which leads generation extracellular deleterious Aβ plaques. Not all steps biogenesis clear so far, these questions should be addressed future studies. complex chronic many factors contribute progression.

Язык: Английский

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Human early-onset dementia caused by DAP12 deficiency reveals a unique signature of dysregulated microglia

Nature Immunology, Год журнала: 2023, Номер 24(3), С. 545 - 557

Опубликована: Янв. 19, 2023

Язык: Английский

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Hotspots and trends of microglia in Alzheimer's disease: a bibliometric analysis during 2000–2022

European journal of medical research, Год журнала: 2024, Номер 29(1)

Опубликована: Янв. 24, 2024

Abstract Background Alzheimer's disease is one common type of dementia. Numerous studies have suggested a correlation between and inflammation. Microglia mainly participate in the inflammatory response brain. Currently, ample evidence has shown that microglia are closely related to occurrence development disease. Objective We opted for bibliometric analysis comprehensively summarize advancements study disease, aiming provide researchers with current trends future research directions. Methods All articles reviews pertaining from 2000 2022 were downloaded through Web Science Core Collection. The results subjected using VOSviewer 1.6.18 CiteSpace 6.1 R2. Results Overall, 7449 publications included. number was increasing yearly. United States published most publications. Harvard Medical School papers all institutions. Journal Alzheimer’s Disease o f Neuroscience journals commonly cited, respectively. Mt Heneka author highest productivity co-citation. After analysis, keywords neuroinflammation, amyloid-beta, inflammation, neurodegeneration. Gut microbiota, extracellular vesicle, dysfunction meta-analysis hotspots at present stage likely continue. Conclusion NLRP3 inflammasome, TREM2, gut mitochondrial dysfunction, exosomes hotspots. relationship microglia-mediated neuroinflammation been focus trend research.

Язык: Английский

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Tetrahydroberberine alleviates high-fat diet-induced hyperlipidemia in mice via augmenting lipoprotein assembly-induced clearance of low-density lipoprotein and intermediate-density lipoprotein

European Journal of Pharmacology, Год журнала: 2024, Номер 968, С. 176433 - 176433

Опубликована: Фев. 16, 2024

Язык: Английский

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Demyelination-derived lysophosphatidylserine promotes microglial dysfunction and neuropathology in a mouse model of Alzheimer’s disease

Cellular and Molecular Immunology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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