Elucidating TREM2's Role in Proliferative Diabetic Retinopathy: A Transcriptomic Approach DOI Creative Commons

Qi Liu,

Ya-Ni Wu,

Wan-Zhao Yi

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 12, 2024

Abstract Background Proliferative diabetic retinopathy (PDR) is a leading cause of vision loss in patients. This study aims to identify novel biomarkers for PDR progression using next-generation sequencing (NGS) transcriptome analysis. Methods We conducted weighted gene co-expression network analysis (WGCNA) on RNA-seq data from 43 post-mortem donor retinas key modules associated with (DR) stages. Differential expression was performed transcriptomes patients and healthy controls. Protein levels retinal tissues streptozotocin (STZ)-induced mouse model were validated immunofluorescence Western blot analyses. Results WGCNA identified the "MEyellow" module, comprising 231 genes, as significantly PDR. Intersection differentially expressed genes revealed 29 common both datasets. Gene ontology (GO) highlighted biological significance these particularly TREM2. Immunofluorescence analyses confirmed upregulation TREM2 microglial marker IBA-1 STZ-induced mice, corroborating its critical role. Conclusions implicated pathogenesis PDR, underscoring potential therapeutic target mitigate disease progression.

Language: Английский

Hepatic danger signaling triggers TREM2 + macrophage induction and drives steatohepatitis via MS4A7-dependent inflammasome activation DOI
Linkang Zhou, Xiaoxue Qiu, Ziyi Meng

et al.

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(738)

Published: March 13, 2024

Metabolic dysfunction–associated steatohepatitis (MASH), formerly known as nonalcoholic (NASH), is an advanced stage of metabolic fatty liver disease. The pathogenic mechanisms MASH center on hepatocyte injury and the ensuing immune response within microenvironment. Recent work has implicated TREM2 + macrophages in various disease conditions, substantial induction NASH-associated (NAMs) serves a hallmark Despite this, through which NAMs contribute to pathogenesis remain poorly understood. Here, we identify membrane-spanning 4-domains a7 (MS4A7) NAM-specific factor that exacerbates progression mice. Hepatic MS4A7 expression was strongly induced mouse human associated with severity injury. Whole-body myeloid-specific ablation Ms4a7 alleviated diet-induced pathologies male We demonstrate exposure lipid droplets (LDs), released upon steatotic hepatocytes, triggered NAM exacerbated MASH-associated MS4A7-dependent manner. Mechanistically, drove NLRP3 inflammasome activation via direct physical interaction shaped disease-associated cell states This reveals LD-MS4A7-NLRP3 axis driver provides insights into role pathogenesis.

Language: Английский

Citations

17
Targeting of TAMs: can we be more clever than cancer cells? DOI Creative Commons
Julia Kzhyshkowska, Jiaxin Shen, Irina Larionova

et al.

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(12), P. 1376 - 1409

Published: Nov. 8, 2024

АBSTRACT: With increasing incidence and geography, cancer is one of the leading causes death, reduced quality life disability worldwide. Principal progress in development new anticancer therapies, improving efficiency immunotherapeutic tools, personification conventional therapies needs to consider cancer-specific patient-specific programming innate immunity. Intratumoral TAMs their precursors, resident macrophages monocytes, are principal regulators tumor progression therapy resistance. Our review summarizes accumulated evidence for subpopulations number biomarkers, indicating predictive value clinical parameters carcinogenesis resistance, with a focus on solid cancers non-infectious etiology. We present state-of-the-art knowledge about tumor-supporting functions at all stages highlight recently identified by single-cell spatial analytical methods, that discriminate between tumor-promoting tumor-inhibiting TAMs, where both subtypes express combination prototype M1 M2 genes. focuses novel mechanisms involved crosstalk among epigenetic, signaling, transcriptional metabolic pathways TAMs. Particular attention has been given link cell metabolism epigenetic histone lactylation, which can be responsible unlimited protumoral Finally, we explain how interfere currently used therapeutics summarize most advanced data from trials, divide into four categories: inhibition TAM survival differentiation, monocyte/TAM recruitment tumors, functional reprogramming genetic enhancement macrophages.

Language: Английский

Citations

14
TREM2 as a Therapeutic Target in Atherosclerosis DOI Open Access

Siting Xu,

Bo Yang,

Wenhua Yu

et al.

Cell Biology International, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

ABSTRACT Atherosclerosis is driven by the expansion of cholesterol‐loaded foamy macrophages in arterial intima. Single‐cell RNA sequencing has recently revealed transcriptional landscape these atherosclerotic plaques and uncovered a population cell‐like myeloid cells expressing triggering receptor expressed on cells‐2 (TREM2)—TREM2 hi macrophages. Fundamental research brought essential insight into significance TREM2 for foam macrophage survival atherosclerosis progression, making as therapeutic target possible. This review retraces TREM2's winding route from pure knowledge to interventions, well potential feasibility its clinical application atherosclerosis.

Language: Английский

Citations

1
Bone marrow breakout lesions act as key sites for tumor-immune cell diversification in multiple myeloma DOI Open Access

Raphael Lutz,

Alexandra M. Poos,

Llorenç Solé‐Boldo

et al.

Science Immunology, Journal Year: 2025, Volume and Issue: 10(104)

Published: Feb. 7, 2025

The bone marrow microenvironment plays a crucial role in the development of multiple myeloma. As disease progresses, malignant myeloma cells can evolve to survive outside marrow. However, processes underlying independence and their consequences for immune control remain poorly understood. Here, we conducted single-cell spatial multiomics analyses marrow-confined intramedullary paired breakout lesions that disrupt cortical bone. These revealed distinct cellular architectural features lesions, characterized by extensive areas plasma interspersed with lesion-specific solitary natural killer macrophage populations, as well focal accumulations cell agglomerates. Within these agglomerates, spatially confined T clones expanded alongside various cells, coinciding local genomic evolution tumor cells. identify hotspot tumor-immune interactions diversification, representing key event pathogenesis.

Language: Английский

Citations

1
The double-edged role and therapeutic potential of TREM2 in atherosclerosis DOI Creative Commons

Botao Zhu,

Yuxuan Liu, Daoquan Peng

et al.

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Nov. 4, 2024

Abstract Atherosclerosis is a chronic lipid-driven inflammatory disease characterized by infiltration of large numbers macrophages. The progression the closely related to status macrophages in atherosclerotic plaques. Recent advances plaque analysis have revealed subpopulation that express high levels triggering receptor expressed on myeloid cells 2 (TREM2). Although TREM2 known play critical role inflammation, lipid metabolism, and tissue repair, its atherosclerosis still not fully understood. studies shown promotes macrophage cholesterol uptake efflux, enhances efferocytosis function, regulates inflammation cell survival, all which are significant functions atherosclerosis. In early plaques increases lesion size. advanced survival stability. dualistic nature atherosclerosis, where it can exert both protective effect side increased size, presents complex but crucial area study. Understanding these dual roles could help development new therapeutic strategies modulate activity utilize atheroprotective function while mitigating deleterious effects. this review, we discuss mechanisms during different stages plaques, as well potential applications diagnosis treatment

Language: Английский

Citations

6
Mechanisms of TREM2 mediated immunosuppression and regulation of cancer progression DOI Creative Commons
Lei Xia,

Ya Ni Gou,

Jin Yong Hao

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: April 25, 2024

Cancer immunotherapy has recently emerged as a key strategy for cancer treatment. TREM2, target regulating the tumor immune microenvironment, is important in treatment and progression. TREM2 an signaling hub that regulates multiple pathological pathways. It not only suppresses anti-tumor responses by inhibiting T cell-mediated responses, but it also influences tumorigenesis affecting NK immunity. Noticeably, expression levels vary significantly among different cells, can regulate progression modulating various Above all, summarizing role of mechanism which progression, this paper clarifies TREM2’s both therapy, identifying new therapeutic oncology diseases.

Language: Английский

Citations

4
Trem2-expressing multinucleated giant macrophages are a biomarker of good prognosis in head and neck squamous cell carcinoma DOI Creative Commons
Grégoire Gessain,

Ahmed-Amine Anzali,

Marvin Lerousseau

et al.

Cancer Discovery, Journal Year: 2024, Volume and Issue: 14(12), P. 2352 - 2366

Published: Sept. 13, 2024

Abstract Patients with head and neck squamous cell carcinomas (HNSCC) often have poor outcomes due to suboptimal risk management treatment strategies; yet integrating novel prognostic biomarkers into clinical practice is challenging. Here, we report the presence of multinucleated giant cells (MGC)—a type macrophages—in tumors from patients HNSCC, which are associated a favorable prognosis in treatment-naive preoperative chemotherapy–treated patients. Importantly, MGC density increased following therapy, suggesting role these antitumoral response. To enable translation as marker, developed deep-learning model automate its quantification on routinely stained pathological whole slide images. Finally, used spatial transcriptomic proteomic approaches describe MGC-related tumor microenvironment observed an increase central memory CD4 T cells. We defined MGC-specific signature resembling TREM2-expressing mononuclear tumor-associated macrophages, colocalized keratin niches. Significance: Novel individual needed guide therapeutic decisions for cancer. first time, granulomas macrophages keratin-rich niches, biomarker slides.

Language: Английский

Citations

4
Role of TREM2 in immune and neurological diseases: Structure, function, and implications DOI
Peng Yin, Zhaoliang Su,

Xiaozheng Shu

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 143, P. 113286 - 113286

Published: Oct. 7, 2024

Language: Английский

Citations

4
Targeting immune checkpoints on myeloid cells: current status and future directions DOI Creative Commons

Chuhan Ma,

Yang Li, Min Li

et al.

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(2)

Published: Jan. 3, 2025

Myeloid cells accumulate extensively in most tumors and play a critical role immunosuppression of the tumor microenvironment (TME). Like T cells, myeloid also express immune checkpoint molecules, which induce immunosuppressive phenotype these cells. In this review, we summarize tumor-promoting function expression four types cells: macrophages, neutrophils, dendritic myeloid-derived suppressor are main components TME. By summarizing research status checkpoints, propose that blocking checkpoints on might be an effective strategy to reverse Moreover, combining nanotechnology, cellular therapy, bispecific antibodies achieve precise targeting can help avoid adverse effects systemic administration, ultimately achieving balance between efficacy safety cancer therapy.

Language: Английский

Citations

0
Deer antler polypeptides inhibit microglial activation via TREM2 to improve behavior and neuroinflammation in CUMS mice DOI
Liping Zhai, Heping Shen, Shasha Wu

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 150, P. 114284 - 114284

Published: Feb. 15, 2025

Language: Английский

Citations

0