Stromal cells direct local differentiation of regulatory dendritic cells
Stromal cells direct local differentiation of regulatory dendritic cells
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DOI：
10.1016/j.immuni.2004.10.012
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发表时间：
2004-12-01
期刊：
影响因子：
32.4
通讯作者：
Kaye, PM
中科院分区：
文献类型：
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作者：
Svensson, M;Maroof, A;Kaye, PM
CD11c（hi）树突状细胞（DC）在细胞介导免疫的启动过程中发挥重要作用。近年来，CD11c(lo)CD45RB(hi) DC具有调控性质。然而，人们对监管DC的起源知之甚少。在这里，我们发现脾脏来源的基质细胞促进来自谱系阴性c-kit（+）祖细胞的CD11c(lo)OCD45RB（+）产生il -10的调节性DC的选择性发育。这些DC在体外具有抑制T细胞反应和诱导产生il -10的调节性T细胞的能力，并在体内诱导抗原特异性耐受。此外，感染多诺瓦利什曼原虫小鼠的基质细胞更有效地支持这些高效调节性DC的分化。因此，组织基质细胞通过调节表型指导DC发育的能力为局部免疫调节提供了一种新的机制。
CD11c(hi) dendritic cells (DC) play an essential role during the initiation of cell-mediated immunity. Recently, CD11c(lo)CD45RB(hi) DC with regulatory properties have been described. However, the origins of regulatory DC are poorly understood. Here, we show that spleen-derived stromal cells promote selective development of CD11c(lo)OCD45RB(+) IL-10-producing regulatory DC from lineage-negative c-kit(+) progenitor cells. These DC have the capacity to suppress T cell responses and induce IL-10-producing regulatory T cells in vitro and to induce antigen -specific tolerance in vivo. Furthermore, stromal cells from mice infected with Leishmania donovani more effectively supported differentiation of these highly potent regulatory DC. The ability of tissue stromal cells to direct the development of DC with a regulatory phenotype thus provides a new mechanism for local immune regulation.