Hepatic Stellate Cells Directly Inhibit B Cells via Programmed Death-Ligand 1.
Hepatic Stellate Cells Directly Inhibit B Cells via Programmed Death-Ligand 1.
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DOI：
10.4049/jimmunol.1501737
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发表时间：
2016-02-15
期刊：
影响因子：
--
通讯作者：
Lin F
中科院分区：
文献类型：
--
作者：
Li Y;Lu L;Qian S;Fung JJ;Lin F
We previously demonstrated that mouse hepatic stellate cells (HSCs) suppress T cells via programmed death-ligand 1 (PD-L1), but whether HSCs exert any effects on B cells, the other component of the adaptive immune system, remains unknown. In this study, we found that mouse HSCs directly inhibited B cells and that PD-L1 was also integrally involved. We found that (a) HSCs inhibited the upregulation of activation markers on activated B cells; (b) HSCs inhibited the proliferation of activated B cells and their cytokine/immunoglobulin production in vitro; and (c) pharmaceutically or genetically blocking the interaction of PD-L1 with programmed death-1 (PD-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 antigen, significantly suppressed antigen-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.
