Oncotarget

Research Papers:

Tumor-specific hepatic stellate cells (tHSCs) induces DIgR2 expression in dendritic cells to inhibit T cells

Yun-Hong Xia _, Zhen Lu, Min Zhao, Wen-Ting Dai, Lu Ding, Li-Xia Hu and Guo-Lin Jiang

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Oncotarget. 2017; 8:55084-55093. https://doi.org/10.18632/oncotarget.19027

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Abstract

Yun-Hong Xia1,*, Zhen Lu2,*, Min Zhao3, Wen-Ting Dai3, Lu Ding3, Li-Xia Hu3 and Guo-Lin Jiang4

1Department of Oncology, The Fourth Affiliated Hospital, Anhui Medical University, Hefei 230022, China

2Department of General Surgery, The Fourth Affiliated Hospital, Anhui Medical University, Hefei 230022, China

3Hefei Hospital, Anhui Medical University, Hefei 230011, China

4Key Laboratory of Anhui Medical University, Hefei 230061, China

*Co-first author

Correspondence to:

Yun-Hong Xia, email: [email protected], [email protected]

Keywords: hepatic stellate cells (tHSCs), hepatocellular carcinoma (HCC), DIgR2, dendritic cells, tumor immunity

Received: May 17, 2017     Accepted: June 16, 2017     Published: July 05, 2017

ABSTRACT

Tumor-specific hepatic stellate cells (tHSCs) contributes to tumorigenesis and progression of hepatocellular carcinoma (HCC). The potential function of tHSCs on dendritic cells (DCs) was studied here. We discovered that tHSCs co-culture induced upregulation of DIgR2 (dendritic cell-derived immunoglobulin receptor 2) in bone marrow-derived DCs (mDCs). Activation of MEK-ERK is required for DIgR2 expression in mDCs. MEK-ERK inhibitors or shRNA-mediated silence of MEK1/2 in mDCs inhibited tHSCs-induced DIgR2 expression. Meanwhile, tHSCs stimulation decreased production of multiple cytokines (CD80, CD86 and IL-12) in mDCs. Such an effect was almost reversed by DIgR2 shRNA in mDCs. Further, tHSCs-stimulated mDCs induced T-cell hypo-responsiveness, leading to decreased cytotoxic T lymphocyte (CTL) activity and reduced IFN-γ production in splenic T cells. T cell proliferation inhibition and apoptosis were also noticed. These actions on T cells were again largely inhibited by DIgR2 shRNA in mDCs. Together, our results indicate that tHSCs directly induces DIgR2 expression in DCs to inhibit T cells.


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