In Vivo Immune Modulatory Activity of Hepatic Stellate Cells in Mice
Open accessAbstract
Accumulating data suggest that hepatic tolerance, initially demonstrated by spontaneous acceptance of liver allografts in many species, results from an immune regulatory activity occurring in the liver. However, the responsible cellular and molecular components have not been completely understood. We have recently described profound T cell inhibitory activity of hepatic stellate cells (HSCs) in vitro . In this study, we demonstrate in vivo evidence of immune modulatory activity of HSCs in mice using an islet transplantation model. Co-transplanted HSCs effectively protected islet allografts from rejection, forming a multi-layered capsule, which reduced allograft immunocyte infiltrates by enhancement of apoptotic death. The immune modulation by HSCs appeared to be a local effect, and regulated by inducible expression of B7-H1, an inhibitory molecule of B7 family. This may reflect an intrinsic mechanism of immune inhibition mediated by liver-derived tissue cells. In conclusion , these results may lead to better understanding of liver immunobiology and development of new strategies for treatment of liver diseases.
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HSCs cull the pool of activated T cells by expressing PD-L1 to induce T cell apoptosis.
“HSCs cull the pool of activated T cells by expressing PD-L1 to induce T cell apoptosis (46–48)”
From Hepatic Stellate Cell-Immune Interactions in NASH (2022) · cites this paper as [47]
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References 43 · Cited by 154
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- Authors
- Chen, C.-H., Kuo, L.-M., Chang, Y., Wu, W., Goldbach, C., Ross, M. A., Stolz, D. B., Chen, L., Fung, J. J., Lu, L., & Qian, S.
- Affiliations
- University of Pittsburgh (US)
- Children's Hospital of Pittsburgh (US)
- Johns Hopkins University (US)
- Cleveland Clinic (US)
- Corresponding author
- Lu, Lin
- Qian, Shiguang
- Venue
- Hepatology
- Published
- 2006-11
- Volume
- 44
- Issue
- 5
- Pages
- 1171-1181
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2073716326
- Cited by
- 154
- References
- 43
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 10 · 2018: 5 · 2017: 4 · 2016: 15 · 2015: 7 · 2014: 14 · 2013: 16 · 2012: 15
- FWCI
- 6.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058316, DK58316)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- hepatic stellate cells, immunomodulation, liver tolerance, islet transplantation, allograft rejection, T cell suppression, PD-L1, apoptosis
- MeSH terms
- Animals, Islets of Langerhans, Kidney, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, T-Lymphocytes, Transplantation, Homologous, Antigens, CD, Islets of Langerhans Transplantation, Hepatocytes, Green Fluorescent Proteins, Mice
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