ArticlePloS one2017
Human intrahepatic ILC2 are IL-13positive amphiregulinpositive and their frequency correlates with model of end stage liver disease score.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 54 citations in OpenAlex.
- Discriminative Role of Interleukin-6, Neuropilin-1, and Amphiregulin for Cirrhosis in Patients with Chronic Hepatitis B Infection.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2026Article
- Innate lymphoid cell heterogeneity and etiology-specific reprogramming in hepatocellular carcinoma.NPJ precision oncology · 2026Article
- Tissue-Resident ILC2s Across Organs: Heterogeneity, Niche Crosstalk, and Shared Regulatory Circuits.Immune network · 2025Review
- Conserved functional features of natural killer cell subsets in chicken, human, and murine immune systems.iScience · 2025Article
- [Research progress on the role of type II innate lymphoid cells in liver diseases].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Review
- Article
- Liver group 2 innate lymphoid cells regulate blood glucose levels through IL-13 signaling and suppression of gluconeogenesis.Nature communications · 2022Article
- Tissue-Dependent Adaptations and Functions of Innate Lymphoid Cells.Frontiers in immunology · 2022Review
- Group-2 Innate Lymphoid Cells Promote HCC Progression Through CXCL2-Neutrophil-Induced Immunosuppression.Hepatology (Baltimore, Md.) · 2021Article
- A crosstalk between type 2 innate lymphoid cells and alternative macrophages in lung development and lung diseases (Review).Molecular medicine reports · 2021Review
- Interleukin-13 as a target to alleviate severe coronavirus disease 2019 and restore lung homeostasis.Journal of clinical and translational research · 2021Article
- Type 2 Innate Lymphoid Cells: Protectors in Type 2 Diabetes.Frontiers in immunology · 2021Review
- Tissue-Specific Molecular Markers and Heterogeneity in Type 2 Innate Lymphoid Cells.Frontiers in immunology · 2021Review
- Natural Killer Cells and Regulatory T Cells Cross Talk in Hepatocellular Carcinoma: Exploring Therapeutic Options for the Next Decade.Frontiers in immunology · 2021Review
- Review
- Review
- Mesenchymal stem cell therapy for liver fibrosis/cirrhosis.Annals of translational medicine · 2020Review
- Reduction of circulating innate lymphoid cell progenitors results in impaired cytokine production by innate lymphoid cells in patients with lupus nephritis.Arthritis research & therapy · 2020Article
- Hepatic ILC2 activity is regulated by liver inflammation-induced cytokines and effector CD4Scientific reports · 2020Article
- Age-Related Dynamics of Circulating Innate Lymphoid Cells in an African Population.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
introductionInnate lymphoid cells (ILC) have been implicated in the initiation of inflammation and fibrosis in mice. However, ILC have not been characterized in inflamed human liver tissue.
methodsHuman intrahepatic lymphocytes were isolated by mechanical digestion and phenotyped by flow cytometry. Conditioned medium from cultures of primary human biliary epithelial cells, stellate cells, fibroblasts and inflamed human liver tissue was used to model the effects of the inflammatory liver environment of ILC phenotype and function.
resultsAll three ILC subsets were present in the human liver, with the ILC1 (CRTH2negCD117neg) subset constituting around 70% of intrahepatic ILCs. Both NCRpos (NKp44+) and NCRneg ILC3 (CRTH2negCD117pos) subsets were also detected. ILC2 (CRTH2pos) frequency correlated with disease severity measured by model of end stage liver disease (MELD) scoring leading us to study this subset in more detail. ILC2 displayed a tissue resident CD69+ CD161++ phenotype and expressed chemokine receptor CCR6 allowing them to respond to CCL20 secreted by cholangiocytes and stellate cells. ILC2 expressed integrins VLA-5 and VLA-6 and the IL-2 and IL-7 cytokine receptors CD25 and CD127 although IL-2 and IL-7 were barely detectable in inflamed liver tissue. Although biliary epithelial cells secrete IL-33, intrahepatic ILC2 had low expression of the ST2 receptor. Intrahepatic ILC2 secreted the immunoregulatory and repair cytokines IL-13 and amphiregulin.
conclusionsIntrahepatic ILC2 express receptors allowing them to be recruited to bile ducts in inflamed portal tracts. Their frequencies increased with worsening liver function. Their secretion of IL-13 and amphiregulin suggests they may be recruited to promote resolution and repair and thereby they may contribute to ongoing fibrogenesis in liver disease.
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