ArticleGastroenterology2014
Interleukin 17-producing γδT cells promote hepatic regeneration in mice.
Article in Gastroenterology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 77 citations in OpenAlex.
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- Diverse Subsets of γδT Cells and Their Specific Functions Across Liver Diseases.International journal of molecular sciences · 2025Review
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Hepatoprotective effect of Paederia foetida on paracetamol-induced hepatobiliary disease in rats via alteration of inflammatory and Nrf2/HO-1 pathway.Acta cirurgica brasileira · 2025Article
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- A small molecule MST1/2 inhibitor accelerates murine liver regeneration with improved survival in models of steatohepatitis.PNAS nexus · 2024Article
- Ten-eleven translocation-2-mediated macrophage activation promotes liver regeneration.Cell communication and signaling : CCS · 2024Article
- Characteristics of circulating immune cells in HBV-related acute-on-chronic liver failure following artificial liver treatment.BMC immunology · 2023Article
- Liver Regeneration and Immunity: A Tale to Tell.International journal of molecular sciences · 2023Review
- The Tumor Microenvironment of Hepatocellular Carcinoma: Untying an Intricate Immunological Network.Cancers · 2022Review
- Trans-activation of eotaxin-1 by Brg1 contributes to liver regeneration.Cell death & disease · 2022Article
- Intrahepatic microbes govern liver immunity by programming NKT cells.The Journal of clinical investigation · 2022Article
- Dectin-1 Signaling Update: New Perspectives for Trained Immunity.Frontiers in immunology · 2022Review
- LR12 Promotes Liver Repair by Improving the Resolution of Inflammation and Liver Regeneration in Mice with Thioacetamide- (TAA-) Induced Acute Liver Failure.Mediators of inflammation · 2021Article
- Nitric Oxide Regulates Macrophage Fungicidal ActivityApplied in vitro toxicology · 2020Article
- Natural Self-Ligand Gamma Delta T Cell Receptors (γδTCRs) Insight: The Potential of Induced IgG.Vaccines · 2020Article
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsSubsets of leukocytes synergize with regenerative growth factors to promote hepatic regeneration. γδT cells are early responders to inflammation-induced injury in a number of contexts. We investigated the role of γδT cells in hepatic regeneration using mice with disruptions in Tcrd (encodes the T-cell receptor δ chain) and Clec7a (encodes C-type lectin domain family 7 member a, also known as DECTIN1).
methodsWe performed partial hepatectomies on wild-type C57BL/6, CD45.1, Tcrd(-/-), or Clec7a(-/-) mice. Cells were isolated from livers of patients and mice via mechanical and enzymatic digestion. γδT cells were purified by fluorescence-activated cell sorting.
resultsIn mice, partial hepatectomy up-regulated expression of CCL20 and ligands of Dectin-1, which was associated with recruitment and activation of γδT cells and their increased production of interleukin (IL)-17 family cytokines. Recruited γδT cells induced production of IL-6 by antigen-presenting cells and suppressed expression of interferon gamma by natural killer T cells, promoting hepatocyte proliferation. Absence of IL-17-producing γδT cells or deletion of Dectin-1 prevented development of regenerative phenotypes in subsets of innate immune cells. This slowed liver regeneration and was associated with reduced expression of regenerative growth factors and cell cycle regulators. Conversely, exogenous administration of IL-17 family cytokines or Dectin-1 ligands promoted regeneration. More broadly, we found that γδT cells are required for inflammatory responses mediated by IL-17 and Dectin-1.
conclusionsγδT cells regulate hepatic regeneration by producing IL-22 and IL-17, which have direct mitogenic effects on hepatocytes and promote a regenerative phenotype in hepatic leukocytes, respectively. Dectin-1 ligation is required for γδT cells to promote hepatic regeneration.
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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.