ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Hepatic stellate cells preferentially induce Foxp3+ regulatory T cells by production of retinoic acid.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 138 citations in OpenAlex.
- Regulatory T Cells in Hepatocellular Carcinoma: Spatial Niches, Biomarkers, and Clinical Implications.International journal of molecular sciences · 2026Review
- Peptide aptamer sP10 targeting NPM1 attenuates liver fibrosis and hepatocellular carcinoma.Journal of translational medicine · 2026Article
- Clinical applications of immunogenomics in hepatocellular carcinoma.Clinical and molecular hepatology · 2026Review
- The double-edged sword of regulatory T cells in MASLD: from inflammation control to fibrosis promotion.Animal cells and systems · 2026Review
- Liver microenvironment-driven immunosuppressive niche in colorectal cancer liver metastasis and its therapeutic remodeling.Frontiers in immunology · 2026Review
- NAFLD-associated immune remodeling in colorectal cancer liver metastasis: mechanisms and implications for immunotherapy.Frontiers in immunology · 2026Review
- Th2 Suppression Through Antigen Liver Expression Using mRNA-LNP Technology.Biomedicines · 2025Article
- Antifibrotic therapies for metabolic dysfunction-associated steatotic liver disease.JHEP reports : innovation in hepatology · 2025Review
- Hepatic stellate cells: balancing homeostasis, hepatoprotection and fibrogenesis in health and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- Vitamin A Metabolism and Resistance of Hepatic Metastases to Immunotherapy.Molecular cancer therapeutics · 2025Review
- Hepatic Stellate Cells Functional Heterogeneity in Liver Cancer.Seminars in liver disease · 2025Review
- Plasma Extracellular Vesicle-derived MicroRNA Associated with Human Alpha-1 Antitrypsin Deficiency-mediated Liver Disease.Journal of clinical and translational hepatology · 2025Article
- Inflammation and Immunity in Liver Neoplasms: Implications for Future Therapeutic Strategies.Molecular cancer therapeutics · 2025Review
- Dynamic crosstalk between HSCs and liver microenvironment: multicellular interactions in the regulation of liver fibrosis.Frontiers in cell and developmental biology · 2025Review
- Immunomodulatory role of vitamin D and emerging immunotherapies in hepatocellular carcinoma.Frontiers in nutrition · 2025Review
- Immune Checkpoint Inhibitors in Hepatocellular Carcinoma and Their Hepatic-Related Side Effects: A Review.Cancers · 2024Review
- Treatment Options for Hepatocellular Carcinoma Using Immunotherapy: Present and Future.Journal of clinical and translational hepatology · 2024Review
- Liver-Targeting Nanoplatforms for the Induction of Immune Tolerance.Nanomaterials (Basel, Switzerland) · 2023Review
- Nonalcoholic steatohepatitis-related hepatocellular carcinoma: pathogenesis and treatment.Nature reviews. Gastroenterology & hepatology · 2023Review
- Mechanisms of Resistance to Immunotherapy in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2023Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The liver has long been described as immunosuppressive, although the mechanisms underlying this phenomenon are incompletely understood. Hepatic stellate cells (HSCs), a population of liver nonparenchymal cells, are potent producers of the regulatory T cell (Treg)-polarizing molecules TGF-β1 and all-trans retinoic acid, particularly during states of inflammation. HSCs are activated during hepatitis C virus infection and may therefore play a role in the enrichment of Tregs during infection. We hypothesized that Ag presentation in the context of HSC activation will induce naive T cells to differentiate into Foxp3(+) Tregs. To test this hypothesis, we investigated the molecular interactions between murine HSCs, dendritic cells, and naive CD4(+) T cells. We found that HSCs alone do not present Ag to naive CD4(+) T cells, but in the presence of dendritic cells and TGF-β1, preferentially induce functional Tregs. This Treg induction was associated with retinoid metabolism by HSCs and was dependent on all-trans retinoic acid. Thus, we conclude that HSCs preferentially generate Foxp3(+) Tregs and, therefore, may play a role in the tolerogenic nature of the liver.
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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.