Hepatic Stellate Cells Directly Inhibit B Cells via Programmed Death–Ligand 1
Open accessAbstract
We demonstrated previously that mouse hepatic stellate cells (HSCs) suppress T cells via programmed death–ligand 1 (PD-L1), but it remains unknown whether they exert any effects on B cells, the other component of the adaptive immune system. In this study, we found that mouse HSCs directly inhibited B cells and that PD-L1 was also integrally involved. We found that HSCs inhibited the upregulation of activation markers on activated B cells, as well as the proliferation of activated B cells and their cytokine/Ig production in vitro, and that pharmaceutically or genetically blocking the interaction of PD-L1 with programmed cell death protein 1 impaired the ability of HSCs to inhibit B cells. To test the newly discovered B cell–inhibitory activity of HSCs in vivo, we developed a protocol of intrasplenic artery injection to directly deliver HSCs into the spleen. We found that local delivery of wild-type HSCs into the spleens of mice that had been immunized with 4-hydroxy-3-nitrophenylacetyl–Ficoll, a T cell–independent Ag, significantly suppressed Ag-specific IgM and IgG production in vivo, whereas splenic artery delivery of PD-L1–deficient HSCs failed to do so. In conclusion, in addition to inhibiting T cells, mouse HSCs concurrently inhibit B cells via PD-L1. This direct B cell–inhibitory activity of HSCs should contribute to the mechanism by which HSCs maintain the liver’s immune homeostasis.
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HSC-expressed PD-L1 may contribute to the inhibition of T-cell- and B-cell-mediated immune responses.
“Moreover, HSC-expressed PD-L1 may contribute to the inhibition of T-cell- and B-cell-mediated immune responses [251, 252].”
From Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells (2025) · cites this paper as [251]
The expression of TGFβ and PD-L1 by HSCs and HSC-derived cancer-associated fibroblasts (CAFs) may downregulate T-cell-mediated immune responses and increase regulatory T cells.
“The expression of TGFβ and PD-L1 by HSCs and HSC-derived cancer-associated fibroblasts (CAFs) may downregulate T-cell-mediated immune responses and increase regulatory T cells [236, 251, 252, 281–283].”
From Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells (2025) · cites this paper as [251]
HSCs may oppose B cell activity via the same PD-L1 mechanism.
“Remarkably, HSCs may oppose B cell activity via the same mechanism (49).”
From Hepatic Stellate Cell-Immune Interactions in NASH (2022) · cites this paper as [49]
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Hepatic Stellate Cell-Immune Interactions in NASH
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- Authors
- Li, Y., Lu, L., Qian, S., Fung, J. J., & Lin, F.
- Affiliations
- Cleveland Clinic (US)
- Department of Immunology, Lerner Research Institute , Cleveland Clinic, Cleveland, OH 44195
- Corresponding author
- Li, Yan
- Qian, Shiguang
- Lin, Feng
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-02
- Volume
- 196
- Issue
- 4
- Pages
- 1617-1625
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC4784705
- OpenAlex
- W2233668667
- Cited by
- 29
- References
- 49
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 2
- FWCI
- 1.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR061564, R01AR061564)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- hepatic stellate cells, B cells, PD-L1, PD-1, B cell suppression, antibody production, T-independent antigens, liver fibrosis
- MeSH terms
- Animals, B-Lymphocytes, Ficoll, Homeostasis, Immunoglobulin G, Immunoglobulin M, Liver, Lymphocyte Activation, Mice, Inbred C57BL, Spleen, Mice, Knockout, Hepatic Stellate Cells, B7-H1 Antigen, Programmed Cell Death 1 Receptor
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