Ask about this productRelated genes to: TREM2 antibody
- Gene:
- TREM2 NIH gene
- Name:
- triggering receptor expressed on myeloid cells 2
- Previous symbol:
- -
- Synonyms:
- TREM-2, Trem2a, Trem2b, Trem2c
- Chromosome:
- 6p21.1
- Locus Type:
- gene with protein product
- Date approved:
- 2002-08-09
- Date modifiied:
- 2019-04-23
Related products to: TREM2 antibody
Related articles to: TREM2 antibody
- Complex molecular mechanisms underlie the heterogeneity of microglia immune functions in neurodegenerative diseases. Here, we report on the transcriptional mechanisms that control microglial activities associated with demyelination in mice. Using flow cytometry, microscopy, and RNA-seq, we identify two dominant states of inflammatory microglia: Clec7aCD229CD11c microglia, which are prone to proliferation and express high mRNA levels of Fn1 and Vegfa, and Clec7aCD229CD11c microglia, which are characterized by prominent mRNA expression of tissue-remodeling and antigen presentation effectors. Achieving these states implicates genome-wide nucleosome remodeling, which is driven by state-dependent stimulation of transcription factors such as Pu.1, AP-1, C/ebp, Mef2, and Egr2. Notably, an H3K27me3-based gatekeeping mechanism controls expression of key regulators, including Egr2. Mechanistically, we validate the relevance of Trem2, Mef2a, and Egr2 to the inflammatory microglial polarization process. Therefore, distinct configurations of signals, along with chromatin remodeling, orchestrate transcription in microglia to support their immune activities in the context of demyelination. - Source: PubMed
Publication date: 2026/06/18
Distéfano-Gagné FélixBelhamiti NesrineSaxon WilliamBitarafan SaraXavier André MachadoFiola StéphanieRivest SergeGosselin David - Aging is the strongest risk factor for Alzheimer's disease (AD), a multifactorial neurodegenerative disorder characterized by amyloid-β (Aβ) accumulation, tau pathology (hyperphosphorylated tau and neurofibrillary tangles [NFTs]), and associated neuroinflammatory processes. Age-related cellular and molecular stressors, including mitochondrial dysfunction, genomic instability, and chronic low-grade inflammation, progressively increase vulnerability to neurodegeneration. In parallel, sex is increasingly recognized as a biological variable that shapes AD risk, clinical course, and neuropathological burden. Women account for roughly two-thirds of AD cases, a disparity not fully explained by longevity. Multiple factors likely contribute, including hormonal transitions across the lifespan (particularly menopausal estrogen decline), sex chromosome-linked immune regulation, sex-dependent interactions between genetic risk factors (e.g., APOE4 and TREM2) and brain aging, and differences in vascular risk, cognitive reserve, and sociocultural exposures that influence disease expression and detection. Microglia, the brain's resident immune cells, are sexually dimorphic, and respond to Aβ and tau pathology, modulating inflammatory signaling, synaptic remodeling, and neurovascular dysfunction implicated in AD. Emerging human and experimental evidence indicate that microglial activation states, immunometabolism, and functional responses differ between males and females and may contribute to sex-specific AD trajectories. Here, we synthesize current evidence supporting microglial sexual dimorphism across aging and AD, highlight possible candidates (hormonal signaling, immuno-aging, disease-associated microglial states, and immunometabolic remodeling), and discuss key knowledge gaps toward sex-informed precision approaches for prevention and treatment. - Source: PubMed
Publication date: 2026/06/18
Figueiredo Emilly VAzevedo Caroline VieiraPenitente Arlete RitaPedrosa Vinicius RCamilo da Silva Vinicius RLongo Beatriz Monteiro - Nasu-Hakola disease is a rare autosomal recessive disorder characterized by progressive cognitive decline and bone cyst formation and is commonly associated with triggering receptor expressed on myeloid cells 2 () variants. Herein, we report a novel frameshift variant in a middle-aged man from a consanguineous Chinese family who presented with early-onset dementia and right ankle pain. Neuroimaging and skeletal examinations revealed cerebral atrophy and bone cystic lesions. Whole-exome sequencing followed by Sanger confirmation identified a homozygous c.257del (p.D86Afs*103) variant. The patient was diagnosed with Nasu-Hakola disease, and his cognitive deterioration continued despite treatment with donepezil and memantine. Functional assays in human embryonic kidney 293T cells demonstrated preserved mRNA expression of the mutant construct but markedly reduced protein levels compared with that of wild-type. We also conducted a descriptive literature review of 54 previously reported cases of homozygous or compound heterozygous variants to highlight the variability in neurodegenerative and skeletal phenotypes. To the best of our knowledge, this is the first report of a c.257del variant in a Chinese family. Our findings expand the mutational spectrum of Nasu-Hakola disease and highlight substantial phenotypic heterogeneity, emphasizing the importance of early genetic testing in patients with unexplained early-onset dementia, even in the absence of bone lesions. - Source: PubMed
Publication date: 2026/06/18
Liu QianLin Rong-RongGao Pei-RongChen Dian-FuLi Hong-Lei - Metabolically-dysfunction-associated steatohepatitis (MASH) is characterised by embryonic Kupffer cell (emKC) loss and proinflammatory macrophage infiltration. While iron dysregulation is implicated in MASH, the role of labile iron (Fe2 + ) in mediating emKC survival and function remains unknown. In human and mouse MASLD/MASH livers, emKCs exhibit repressed iron metabolism, reduced labile iron pools, and mitochondrial dysfunction. KC-specific ferroportin knockout mice recapitulate these defects, accelerating Western diet-induced steatosis and fibrosis. Conversely, ferritin depletion restores emKC labile iron levels, mitigates mitochondrial damage, and attenuates disease severity. Fe2+ deficiency blunts Trem2 expression, whereas restoring Fe2+ homeostasis elevates emKC Trem2 abundance in MASH liver. Weight loss reverses hepatic iron dysfunction and restores emKC homeostasis. Our findings establish labile iron deficiency as a key driver of emKC loss and functional switch in MASH, linking iron metabolism to mitochondrial fitness and inflammation. Targeting emKC iron homeostasis could offer novel therapeutic strategies for MASLD/MASH. - Source: PubMed
Publication date: 2026/06/18
Wang KeAn GaramPark JunhoCunha E Rocha KarinaZeng ZixuanQin HoujiFarrell AndreaSchlotthauer AlexLim WhasunYing Wei - TREM2-expressing scar-associated macrophages (SAMs) are integral to the pathogenesis of hepatic fibrosis; however, the limited understanding of their differentiation and pro-fibrotic functions impedes the advancement of targeted therapeutic strategies. - Source: PubMed
Publication date: 2026/06/16
Yang FanYang WenjingZhang YingYe WenqianZhao JunkangLi RuiChen YurongWang QiyanYuan HongxiaFeng XiueLi Qingshan