ArticleHuman molecular genetics2020
Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions.
Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
What it found
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Who cites it
127 citing papers in PubMed, 206 citations in OpenAlex.
- Clinical considerations for immune dysregulation and immunodeficiency in Down syndrome.Journal of human immunity · 2026Review
- Trem2 regulates macrophage phenotype via the JAK2/STAT3 signaling pathway to ameliorate ventricular remodeling after acute myocardial infarction.Molecular biology reports · 2026Article
- Distinct Transcriptomic Signatures of HIV-1 Tat and gp120 Uncover Differential Neuroimmune Vulnerability in aCurrent issues in molecular biology · 2026Article
- The roles of microglia and astrocytes in inflammasomes and neurological disorders.Neural regeneration research · 2026Article
- Long-Chain S-Acylation Is a Key Modulator During the Macrophage Inflammatory Response.Molecular & cellular proteomics : MCP · 2026Article
- Role Shift of Glial Cells from Physiology to Pathology in Alzheimer's Disease: The Regulatory Impact of Exercise.Neuroscience bulletin · 2026Review
- Correlation of serum glial fibrillary acidic protein (GFAP) and soluble triggering receptor expressed on myeloid cells-2 (sTREM-2) levels with disability and clinical characteristics in multiple sclerosis.Acta neurologica Belgica · 2026Article
- Labile iron starvation in embryonic Kupffer cells aggravates MASH via mitochondrial failure and macrophage dysfunction.Cell death & disease · 2026Article
- Brain-targeted delivery of siRNA via non-viral delivery systems, the therapeutic strategy for Alzheimer's disease-Unveiling challenges and prospects.International journal of pharmaceutics: X · 2026Review
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- Review
- The impact of Trem2-mediated macrophage polarization on the mechanisms of allergic rhinitis.Scientific reports · 2026Article
- Inflammatory-neurodegenerative crosstalk in pediatric severe traumatic brain injury: a multi-domain plasma proteomic study.Molecular medicine (Cambridge, Mass.) · 2026Article
- The role of DAP12 in immune-related inflammatory diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- A Mouthful of Genomic Data: Single-Cell Insights into Salivary Gland Biology and Disease.Biology · 2026Review
- Environmental enrichment modulates chronic poststroke inflammation and links white matter TREM2-positive microglia in recovery in mice.Neuroprotection (Chichester, England) · 2026Article
- Cholecalciferol (vitamin D3) is an agonist of the Alzheimer's disease-associated immune receptor TREM2.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Immuno-Regulation of Brain Region-Specific Organoids Containing Isogenic Microglia-Like Cells.Advanced healthcare materials · 2026Article
- Synthetic cleavage-resistant TREM2 boosts macrophage efferocytosis to treat inflammatory diseases.Cell reports. Medicine · 2026Article
- Impaired TGFβ Signaling in Plaque-Associated Microglia.Biomolecules · 2026Article
67 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Genome-wide association studies have reported that, amongst other microglial genes, variants in TREM2 can profoundly increase the incidence of developing Alzheimer's disease (AD). We have investigated the role of TREM2 in primary microglial cultures from wild type mice by using siRNA to decrease Trem2 expression, and in parallel from knock-in mice heterozygous or homozygous for the Trem2 R47H AD risk variant. The prevailing phenotype of Trem2 R47H knock-in mice was decreased expression levels of Trem2 in microglia, which resulted in decreased density of microglia in the hippocampus. Overall, primary microglia with reduced Trem2 expression, either by siRNA or from the R47H knock-in mice, displayed a similar phenotype. Comparison of the effects of decreased Trem2 expression under conditions of lipopolysaccharide (LPS) pro-inflammatory or IL-4 anti-inflammatory stimulation revealed the importance of Trem2 in driving a number of the genes up-regulated in the anti-inflammatory phenotype. RNA-seq analysis showed that IL-4 induced the expression of a program of genes including Arg1 and Ap1b1 in microglia, which showed an attenuated response to IL-4 when Trem2 expression was decreased. Genes showing a similar expression profile to Arg1 were enriched for STAT6 transcription factor recognition elements in their promoter, and Trem2 knockdown decreased levels of STAT6. LPS-induced pro-inflammatory stimulation suppressed Trem2 expression, thus preventing TREM2's anti-inflammatory drive. Given that anti-inflammatory signaling is associated with tissue repair, understanding the signaling mechanisms downstream of Trem2 in coordinating the pro- and anti-inflammatory balance of microglia, particularly mediating effects of the IL-4-regulated anti-inflammatory pathway, has important implications for fighting neurodegenerative disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.