title: Hepatic Stellate Cells Directly Inhibit B Cells via Programmed Death-Ligand 1.
abstract: 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.
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195; and.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195; and Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195.
authors.forename: Lina
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195; and Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195.
authors.forename: Shiguang
authors.initials: S
authors.lastname: Qian
authors.affiliation: Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195.
authors.forename: John J
authors.initials: JJ
authors.lastname: Fung
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195; and linf2@ccf.org.
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D060890:B7-H1 Antigen / Q000276:immunology* / Q000378:metabolism*; D005362:Ficoll / Q000031:analogs & derivatives / Q000276:immunology; D055166:Hepatic Stellate Cells / Q000276:immunology*; D006706:Homeostasis; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008099:Liver / Q000276:immunology; D008213:Lymphocyte Activation; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics; D013154:Spleen / Q000276:immunology
chemical_list: C516150:(4-hydroxy-3-nitrophenyl)acetyl-Ficoll; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D061026:Programmed Cell Death 1 Receptor; D005362:Ficoll