ArticleImmunity2023
Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development.
Article in Immunity, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers.
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Who cites it
167 citing papers in PubMed, 203 citations in OpenAlex.
- Targeted inhibition of inflammatory liver macrophages with a multifunctional nanoparticle ameliorates metabolic dysfunction-associated steatohepatitis.Bioactive materials · 2027Article
- Metabolic drivers of MASLD and MASH: from hormonal imbalance to fibrosis.Diabetologia · 2026Review
- A Conserved Macrophage-to-Hepatic Stellate Cell PDGF Axis in Human MASH Identified by Multi-Cohort sc/snRNA-Seq Re-Analysis.International journal of molecular sciences · 2026Article
- TREM2-mediated Crosstalk in ALS: Microglial Fate Transition, Protein Aggregate Clearance, and Peripheral Nerve Repair.Neuroscience bulletin · 2026Article
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- Molecular mechanisms and pathogenesis of MASH.Nature · 2026Review
- DAMPs, PAMPs, and Alarmins: From Mechanism to Therapy.MedComm · 2026Review
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- Cancer-associated adipocytes: metabolic reprogramming, crosstalk and therapeutic implications in tumor progression.Signal transduction and targeted therapy · 2026Review
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- TREM2-Targeting peptide tracer for neuroinflammation PET imaging.European journal of nuclear medicine and molecular imaging · 2026Article
- Bile acid retention in efferocytic macrophages shapes their inflammatory status during cholangitis.The Journal of experimental medicine · 2026Article
- 4-Octyl Itaconate Promotes Diabetic Wound Healing by Enhancing Pro-Resolving Macrophages via the Efferocytosis-MCT1-Lactate-GPR132 Pathway and Macrophage-Independent Synergistic Effects.Diabetes & metabolism journal · 2026Article
- Labile iron starvation in embryonic Kupffer cells aggravates MASH via mitochondrial failure and macrophage dysfunction.Cell death & disease · 2026Article
- Review
- Therapeutic potential of glycyrrhizic acid in inflammation-related diseases: from HMGB1-oriented molecular insights to preclinical application.Archives of pharmacal research · 2026Review
- A Versatile In Vitro Quantitative Assay for Macrophage Efferocytosis in Diverse Research Applications.Bio-protocol · 2026Article
- Review
- Triangulating the link between depression and liver disease: An integrative analysis of genetic, observational, and research trend data.Comprehensive psychoneuroendocrinology · 2026Article
- Gestational Melatonin Supplementation Attenuates Maternal Sleep Deprivation-Induced Steatohepatitis Susceptibility in Offspring.Cell proliferation · 2026Article
107 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 6 institutions in 2 countries.
Funding
Abstract
Obesity-induced chronic liver inflammation is a hallmark of nonalcoholic steatohepatitis (NASH)-an aggressive form of nonalcoholic fatty liver disease. However, it remains unclear how such a low-grade, yet persistent, inflammation is sustained in the liver. Here, we show that the macrophage phagocytic receptor TREM2, induced by hepatocyte-derived sphingosine-1-phosphate, was required for efferocytosis of lipid-laden apoptotic hepatocytes and thereby maintained liver immune homeostasis. However, prolonged hypernutrition led to the production of proinflammatory cytokines TNF and IL-1β in the liver to induce TREM2 shedding through ADAM17-dependent proteolytic cleavage. Loss of TREM2 resulted in aberrant accumulation of dying hepatocytes, thereby further augmenting proinflammatory cytokine production. This ultimately precipitated a vicious cycle that licensed chronic inflammation to drive simple steatosis transition to NASH. Therefore, impaired macrophage efferocytosis is a previously unrecognized key pathogenic event that enables chronic liver inflammation in obesity. Blocking TREM2 cleavage to restore efferocytosis may represent an effective strategy to treat NASH.
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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.