Hepatic stroma-educated regulatory DCs suppress CD8(+) T cell proliferation in mice.
Hepatic stroma-educated regulatory DCs suppress CD8(+) T cell proliferation in mice.
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肝基质培养的调节性 DC 抑制小鼠 CD8 T 细胞增殖
DOI：
10.18632/oncotarget.18459
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发表时间：
2017-11-07
期刊：
影响因子：
--
通讯作者：
Song W
中科院分区：
文献类型：
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作者：
Wang Q;He H;Chen D;Wang C;Xu Y;Song W
肝树突状细胞（DC）显示免疫抑制活性并抑制CD 4 + T细胞应答。本研究评估了肝脏DC是否以及如何抑制CD 8 + T细胞。我们发现，骨髓来源的成熟DC与肝基质细胞孵育的特点是寿命较长，CD 11 c，IA/IE，CD 80，CD 86和CD 40表达减少，CD 11b表达增加。这些独特的肝基质细胞训练的成熟DC（LSed-DC）刺激CD 8 + T细胞表达CD 25和CD 69，但抑制其增殖。CD 8 + T细胞的抑制依赖于LSed-DCs释放的可溶性因子，而不是细胞-细胞接触。与成熟DCs相比，LSed-DCs产生更多的NO和IL-10。添加一氧化氮合酶抑制剂PBIT，而不是IL-10阻断mAb，逆转了LSed-DC对CD 8 + T细胞增殖的抑制。我们还发现，LSed-DCs减少了自身免疫性肝炎小鼠模型中CD 8 + T细胞介导的肝损伤。这些结果表明，肝基质诱导成熟DC分化为抑制CD 8 + T细胞增殖的调节性DC，从而有助于肝耐受。
Liver dendritic cells (DCs) display immunosuppressive activities and inhibit the CD4+ T cell response. The present study assessed whether and how liver DCs suppress CD8+ T cells. We found that bone marrow-derived mature DCs incubated with liver stromal cells were characterized by a longer life span, reduced CD11c, IA/IE, CD80, CD86, and CD40 expression, and increased CD11b expression. These unique liver stromal cell-educated mature DCs (LSed-DCs) stimulated CD8+ T cells to express CD25 and CD69, but inhibited their proliferation. CD8+ T cell suppression depended on soluble factors released by LSed-DCs, but not cell-cell contact. Compared with mature DCs, LSed-DCs produced more nitric oxide and IL-10. Addition of a nitric oxide synthase inhibitor, PBIT, but not an IL-10-blocking mAb, reversed LSed-DC inhibition of CD8+ T cell proliferation. We also found that LSed-DCs reduced CD8+ T cell-mediated liver damage in a mouse model of autoimmune hepatitis. These results demonstrate that the liver stroma induces mature DCs to differentiate into regulatory DCs that suppress CD8+ T cell proliferation, and thus contribute to liver tolerance.