ArticleCellular & molecular immunology2021
Kupffer cell restoration after partial hepatectomy is mainly driven by local cell proliferation in IL-6-dependent autocrine and paracrine manners.
Article in Cellular & molecular immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 46 citations in OpenAlex.
- Succinic acid inhibits hepatocyte regenerative signaling via STAT3 SH2-domain engagement.Molecular biomedicine · 2026Article
- Kupffer cells in liver homeostasis and disease: from immune sentinels to metabolic gatekeepers.Nature reviews. Immunology · 2026Review
- Zone-specific hepatocytes orchestrate the early onset of host immune defenses duringFrontiers in immunology · 2026Article
- PINK1/Parkin promotes liver regeneration via Sigma-1 ubiquitination to inhibit ER-Mitochondrial calcium transfer.Theranostics · 2026Article
- Liver macrophages: development, dynamics, and functions.Cellular & molecular immunology · 2025Review
- Harnessing Distinct Tissue-Resident Immune Niches via S100A9/TLR4 Improves Ketone, Lipid, and Glucose Metabolism.Endocrinology · 2025Article
- A historical perspective of Kupffer cells in the context of infection.Cell and tissue research · 2025Review
- NLRP3 inflammasome constrains liver regeneration through impairing MerTK-mediated macrophage efferocytosis.Science advances · 2025Article
- Hepatocyte-derived tissue extracellular vesicles safeguard liver regeneration and support regenerative therapy.Journal of nanobiotechnology · 2024Article
- Liver macrophages revisited: The expanding universe of versatile responses in a spatiotemporal context.Hepatology communications · 2024Review
- The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases.Experimental hematology & oncology · 2024Review
- Ten-eleven translocation-2-mediated macrophage activation promotes liver regeneration.Cell communication and signaling : CCS · 2024Article
- Fate-Mapping Macrophages: From Ontogeny to Functions.Methods in molecular biology (Clifton, N.J.) · 2024Review
- Macrophages clear out necrotic liver lesions: a new magic trick revealed.eGastroenterology · 2023Article
- Does β-Hydroxy-β-Methylbutyrate Have Any Potential to Support the Treatment of Duchenne Muscular Dystrophy in Humans and Animals?Biomedicines · 2023Review
- Monocyte-derived macrophages orchestrate multiple cell-type interactions to repair necrotic liver lesions in disease models.The Journal of clinical investigation · 2023Article
- Spatial dimension of macrophage heterogeneity in liver diseases.eGastroenterology · 2023Review
- Towards using 3D cellular cultures to model the activation and diverse functions of macrophages.Biochemical Society transactions · 2023Review
- Ambiguous Pathogenic Roles of Macrophages in Alcohol-Associated Liver Diseases.Hepatic medicine : evidence and research · 2023Review
- An Eye on Kupffer Cells: Development, Phenotype and the Macrophage Niche.International journal of molecular sciences · 2022Review
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Kupffer cells (KCs), which are liver-resident macrophages, originate from the fetal yolk sac and represent one of the largest macrophage populations in the body. However, the current data on the origin of the cells that restore macrophages during liver injury and regeneration remain controversial. Here, we address the question of whether liver macrophage restoration results from circulating monocyte infiltration or local KC proliferation in regenerating livers after partial hepatectomy (PHx) and uncover the underlying mechanisms. By using several strains of genetically modified mice and performing immunohistochemical analyses, we demonstrated that local KC proliferation mainly contributed to the restoration of liver macrophages after PHx. Peak KC proliferation was impaired in Il6-knockout (KO) mice and restored after the administration of IL-6 protein, whereas KC proliferation was not affected in Il4-KO or Csf2-KO mice. The source of IL-6 was identified using hepatocyte- and myeloid-specific Il6-KO mice and the results revealed that both hepatocytes and myeloid cells contribute to IL-6 production after PHx. Moreover, peak KC proliferation was also impaired in myeloid-specific Il6 receptor-KO mice after PHx, suggesting that IL-6 signaling directly promotes KC proliferation. Studies using several inhibitors to block the IL-6 signaling pathway revealed that sirtuin 1 (SIRT1) contributed to IL-6-mediated KC proliferation in vitro. Genetic deletion of the Sirt1 gene in myeloid cells, including KCs, impaired KC proliferation after PHx. In conclusion, our data suggest that KC repopulation after PHx is mainly driven by local KC proliferation, which is dependent on IL-6 and SIRT1 activation in KCs.
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