Date: Monday, May 4, 2015
Session Time: 4:00pm-5:30pm
Presentation Time: 5:00pm-5:12pm
Location: Room 119-A
Hepatic stellate cells (HSCs) account for one third of the nonparenchymal cells in the liver, which are considered to be critical in maintaining the immunoprivileged status of the liver and induction of liver transplant tolerance. We previously demonstrated that mouse HSCs directly suppress T cells via the surface expression of programmed death-ligand 1 (PD-L1), and indirectly suppress both T and B cells via the induction of myeloid derived suppressor cells, which could be the mechanism by which HSCs sustain the immunosuppressive environment in the liver. However, whether HSCs exert any direct effects on the other components of the adaptive immune system, i.e., B cells, remains unknown. In this study, we demonstrated that, in addition to suppressing T cells, HSCs directly inhibited B cells, a process in which PD-L1 was also integrally involved. In support of these results, we found that (a) HSCs inhibited the upregulation of activation markers upon B cell activation; (b) HSCs inhibited the proliferation of activated B cells; (c) HSCs inhibited antibody production from activated B cells in vitro; and (d) HSCs in which PD-L1 had been blocked by antibodies or HSCs deficient in PD-L1 showed impaired potency in inhibiting activated B cells compared with their controls. To test the newly discovered direct B-cell-inhibitory activity of HSCs in vivo, we developed a protocol of intrasplenic artery injection to locally deliver HSCs directly into the spleen. Using this approach, we demonstrated that local delivery of wild-type HSCs into the spleens of mice that had been immunized with NP-Ficoll, a T-cell-independent antigen, significantly suppressed antigen-specific IgM and IgG production in vivo, whereas splenic artery delivery of PD-L1-knockout HSCs failed to do so. We conclude that, in addition to inhibiting T cells, mouse HSCs directly inhibit B cells via PD-L1. This direct B inhibitory activity of HSCs could be another mechanism contributing to the maintenance of the immune tolerance status of the liver.
Supported in part by grants MDA234458 (FL) and DK84192 (LL)
To cite this abstract in AMA style:Li Y, Fang K, Qian S, Fung J, Lu L, Lin F. Hepatic Stellate Cells Directly Inhibit B Cells Via PD-L1 [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/hepatic-stellate-cells-directly-inhibit-b-cells-via-pd-l1/. Accessed August 25, 2019.
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