Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Institute of Immunology, Hannover Medical School, Hannover, Germany.
Mucosal Immunol. 2014 Mar;7(2):359-68. doi: 10.1038/mi.2013.54. Epub 2013 Aug 14.
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.
从头诱导 Foxp3⁺调节性 T 细胞（Tregs）在肠道引流肠系膜和腹腔淋巴结（mLN 和 celLN）中特别有效。在这里，我们使用淋巴结移植来剖析基质细胞和环境因素对这些 LN 高 Treg 诱导能力的贡献。移植到腘窝后，mLN 和 celLN 保留了其高 Treg 诱导能力，而皮肤引流淋巴结移植到肠道系膜则不能有效诱导 Treg。然而，在没有树突状细胞（DC）的情况下，从头诱导 Treg 被废除，表明这一过程依赖于基质和 DC 的协同贡献。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 移植物没有显示出任何优越的 Treg 诱导能力。总之，我们的观察结果揭示了 LN 基质细胞在从头诱导 Foxp3⁺Tregs 中的一个迄今为止尚未被认识到的作用。
