Pulmonary stromal cells induce the generation of regulatory DC attenuating T-cell-mediated lung inflammation
Pulmonary stromal cells induce the generation of regulatory DC attenuating T-cell-mediated lung inflammation
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DOI：
10.1002/eji.200838542
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发表时间：
2008-10-01
影响因子：
5.4
通讯作者：
Cao, Xuetao
中科院分区：
文献类型：
--
作者：
Li, Qian;Guo, Zhenhong;Cao, Xuetao
组织微环境可能影响DC等免疫细胞的发育和功能。肺间质微环境是否以及如何影响肺树突状细胞的发育和功能，尚需进一步研究。调节性DC(DCreg)可以调节T细胞的反应。我们想知道这种调节性DC是否存在于肺中，以及肺间质微环境对DCreg的产生有何影响。在这里，我们证明了小鼠肺基质细胞可以驱动广泛分布在肺内的未成熟DC增殖和分化为一个独特的DCreg亚群，它高水平表达CD11b，低水平表达MHC II类(I-A)和CD11c，分泌高水平的IL-10、NO和前列腺素E-2(PGE(2))，并抑制T细胞的增殖。在肺中具有相似表型和调节功能的DCreg的天然对应物已经被鉴定。肺间质来源的转化生长因子-β负责将未成熟的DC分化为DCreg，而DCreg来源的PGE2有助于抑制T细胞的增殖。此外，DCreg还能诱导产生CD4(+)CD25(+)Foxp3(+)Treg。重要的是，输注DCreg在体外可以减轻T细胞介导的嗜酸性呼吸道炎症。因此，肺微环境可能驱动DCreg的产生，从而有助于维持免疫稳态，控制肺部炎症。
The tissue microenvironment may affect the development and function of immune cells such as DC. Whether and how the pulmonary stromal microenvironment can affect the development and function of lung DC need to be investigated. Regulatory DC (DCreg) can regulate T-cell response. We wondered whether such regulatory DC exist in the lung and what is the effect of the pulmonary stromal microenvironment on the generation of DCreg. Here we demonstrate that murine pulmonary stromal cells can drive immature DC, which are regarded as being widely distributed in the lung, to proliferate and differentiate into a distinct subset of DCreg, which express high levels of CD11b but low levels of MHC class II (I-A), CD11c, secrete high amounts of IL-10, NO and prostaglandin E-2 (PGE(2)) and suppress T-cell proliferation. The natural counterpart of DCreg in the lung with similar phenotype and regulatory function has been identified. Pulmonary stroma-derived TGF-beta is responsible for the differentiation of immature DC to DCreg, and DCreg-derived PGE2 contributes to their suppression of T-cell proliferation. Moreover, DCreg can induce the generation of CD4(+)CD25(+)Foxp3(+) Treg. Importantly, infusion with DCreg attenuates T-cell-mediated eosinophilic airway inflammation in vitro. Therefore, the pulmonary microenvironment may drive the generation of DCreg, thus contributing to the maintenance of immune homoeostasis and the control of inflammation in the lung.