Activated NKT cells facilitated functional switch of myeloid-derived suppressor cells at inflammation sites in fulminant hepatitis mice

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• 作者：Danxiao Wu^a ; ^b ; ^f ; ¹ ; Yu Shi^c ; ¹ ; Cheng Wang^b ; ^d ; Hanwen Chen^a ; Qiaoyun Liu^a ; Jianhua Liu^b ; Lihuang Zhang^e ; Yihua Wu ; PhD^a ; ^{georgewuer@126.com} ; Dajing Xia ; PhDMD^a ; ^b ; ^{dxia@zju.edu.cn}
• 关键词：BM ; bone marrow ; DC ; dendritic cell ; MDSC ; myeloid-derived suppressor cell ; Treg ; regulatory T cell ; MLN ; mesenteric lymph node ; MNC ; mononuclear cell ; VEGF ; vascular endothelial growth factor ; MFI ; mean fluorescence intensity
• 刊名：Immunobiology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：222
• 期：2
• 页码：440-449
• 全文大小：3144 K
• 卷排序：222

文摘

Myeloid-derived suppressor cells (MDSCs) confer immunosuppressive properties, but their roles in fulminant hepatitis have not been well defined. In this study, we systematically examined the distribution of MDSCs in bone marrow (BM), liver and spleen, and their functional and differentiation status in an acute fulminant hepatitis mouse model induced by lipopolysaccharide and D-galactosamine (LPS-GalN). Moreover, the interaction between NKT cells and MDSCs was determined. Our study revealed that BM contained the largest pool of MDSCs during pathogenesis of fulminant hepatitis compared with liver and spleen. MDSCs in liver/spleen expressed higher levels of chemokine receptors such as CCR2, CX3CR1 and CXCR2. At inflamed tissues such as liver or spleen, activated NKT cells induced differentiation of MDSCs through cell–cell interaction, which markedly dampened the immunosuppressive effects and promoted MDSCs to produce pro-inflammatory cytokines and activate inflammatory cells. Our findings thus demonstrated an unexpected pro-inflammatory state for MDSCs, which was mediated by the activated NKT cells that precipitated the differentiation and functional evolution of these MDSCs at sites of inflammation.