The intestinal micro-environment imprints stromal cells to promote efficient Treg induction in gut-draining lymph nodes

The intestinal micro-environment imprints stromal cells to promote efficient Treg induction in gut-draining lymph nodes
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DOI:
10.1038/mi.2013.54
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发表时间:
2014-03-01
期刊:
影响因子:
8
通讯作者:
Pabst, O.
Pabst, O.
中科院分区:
医学1区
文献类型:
--
作者:
Cording, S.;Wahl, B.;Pabst, O.

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Foxp3(+)调节性T细胞(Tregs)的从头诱导在肠引流肠系膜和腹腔淋巴结(mLN和celLN)中特别有效。在这里,我们使用LN移植来剖析基质细胞和环境因素对LN高treg诱导能力的贡献。移植到腘窝后,mLN和celLN保持了高诱导Treg的能力,而将皮肤引流LN移植到肠系膜后,不能有效诱导Treg。然而,在没有树突状细胞(DC)的情况下,新生Treg诱导被取消,这表明这一过程依赖于基质和DC的协同作用。基质细胞本身受到环境信号的影响,因为来自无菌供体的mLN移植物和来自维生素a缺乏供体的celLN移植物没有表现出任何优越的treg诱导能力。总的来说,我们的观察结果揭示了LN基质细胞在Foxp3(+) Tregs从头诱导中的作用。
De novo induction of Foxp3(+) regulatory T cells (Tregs) is particularly efficient in gut-draining mesenteric and celiac lymph nodes (mLN and celLN). Here we used LN transplantations to dissect the contribution of stromal cells and environmental factors to the high Treg-inducing capacity of these LN. After transplantation into the popliteal fossa, mLN and celLN retained their high Treg-inducing capacity, whereas transplantation of skin-draining LN into the gut mesenteries did not enable efficient Treg induction. However, de novo Treg induction was abolished in the absence of dendritic cells (DC), indicating that this process depends on synergistic contributions of stromal and DC. Stromal cells themselves were influenced by environmental signals as mLN grafts taken from germ-free donors and celLN grafts taken from vitamin A-deficient donors did not show any superior Treg-inducing capacity. Collectively, our observations reveal a hitherto unrecognized role of LN stromal cells for the de novo induction of Foxp3(+) Tregs.