<br>鉴定可选择性扩增调节性 T 细胞的新型 OX40L+ 树突状细胞亚群。,Scientific Reports

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鉴定可选择性扩增调节性 T 细胞的新型 OX40L+ 树突状细胞亚群。
Scientific Reports ( IF 3.8 ) Pub Date : 2018-Oct-08 , DOI: 10.1038/s41598-018-33307-z
Alejandra Marinelarena ₁ , Palash Bhattacharya ₁ , Prabhakaran Kumar ₁ , Ajay V Maker _{1,

2} , Bellur S Prabhakar ₁

Affiliation

我们之前已经证明，GM-CSF 衍生的骨髓树突状细胞 (G-BMDC) 可以通过表面结合分子 OX40L 诱导 Tregs 选择性扩增；然而，这种离体衍生的 DC 子集的生理作用仍有待阐明。我们确定给小鼠施用 GM-CSF 可诱导体内衍生的 OX40L ⁺ DC 在脾脏、肱淋巴结和肝脏中产生，其表型与离体 OX40L ⁺ G-BMDC 相似。 OX40L ⁺ DC 的产生与 GM-CSF 治疗小鼠的脾脏、臂淋巴结和肝脏中功能抑制性 Tregs 的百分比增加相关。来自 GM-CSF 处理小鼠的 DC 以 OX40L 依赖性方式在 CD4 ⁺ T 细胞共培养物中扩增 Treg，表明 OX40L ⁺ DC 可能在外周 Treg 稳态中发挥作用。此外，将 OX40L ⁺ DC 的转录组数据与所有免疫细胞类型的转录组数据进行比较，发现 OX40L ⁺ DC 与稳态免疫细胞不同，并且 OX40L ⁺ G-BMDC 和 OX40L ^- G-BMDC 的微阵列分析显示，与耐受性表型相关的分子，可能在 OX40L ⁺ DC 的功能中发挥重要作用。这些发现表明 OX40L ⁺ DC 可能代表炎症条件下诱导的独特 DC 亚群，可能在维持 Treg 稳态中发挥重要作用。

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Identification of a Novel OX40L+ Dendritic Cell Subset That Selectively Expands Regulatory T cells.

We have previously shown GM-CSF derived bone-marrow dendritic cells (G-BMDCs) can induce the selective expansion of Tregs through the surface-bound molecule OX40L; however, the physiological role of this ex vivo derived DC subset remained to be elucidated. We determined GM-CSF administration to mice induced the generation of in vivo derived OX40L⁺ DCs, phenotypically similar to ex vivo OX40L⁺G-BMDCs, in the spleen, brachial lymph nodes and liver. The generation of OX40L⁺ DCs correlated with increased percentages of functionally suppressive Tregs in the spleen, brachial lymph nodes, and liver of GM-CSF treated mice. DCs from GM-CSF treated mice expanded Tregs in CD4⁺ T-cell co-cultures in an OX40L dependent manner, suggesting OX40L⁺ DCs may play a role in peripheral Treg homeostasis. Furthermore, comparing the transcriptome data of OX40L⁺ DCs to that of all immune cell types revealed OX40L⁺ DCs to be distinct from steady-state immune cells and, microarray analysis of OX40L⁺G-BMDCs and OX40L^-G-BMDCs revealed higher expression of molecules that are associated with tolerogenic phenotype and could play important roles in the function of OX40L⁺ DCs. These findings suggest that OX40L⁺ DCs may represent a unique DC subset induced under inflammatory conditions that may play an essential role in maintaining Treg homeostasis.

更新日期：2018-10-08

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