Crosstalk between bone marrow-derived mesenchymal stem cells and regulatory T cells through a glucocorticoid-induced leucine zipper/developmental endothelial locus-1-dependent mechanism.
Crosstalk between bone marrow-derived mesenchymal stem cells and regulatory T cells through a glucocorticoid-induced leucine zipper/developmental endothelial locus-1-dependent mechanism.
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骨髓间充质干细胞和调节性 T 细胞之间通过糖皮质激素诱导的亮氨酸拉链/发育内皮基因座 1 依赖性机制进行串扰。
DOI：
10.1096/fj.15-273664
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Shi,Xing-Ming
中科院分区：
文献类型：
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作者：
Yang,Nianlan;Baban,Babak;Isales,CarlosM;Shi,Xing-Ming
骨髓是调节性T（Treg）细胞的储存库，但Treg细胞在该环境中如何调节仍然知之甚少。我们发现，糖皮质激素（GC）诱导的亮氨酸拉链（GILZ）在骨髓间充质细胞系细胞或骨髓间充质干细胞（BMSCs）的表达增加了Treg细胞的产生，通过一种机制，涉及上调发育内皮基因座-1（Del-1），一种内源性白细胞-内皮细胞粘附抑制剂。我们发现，GILZ转基因（Tg）小鼠骨组织中Del-1的表达增加了1.4倍，并且这种增加与IL-10的产生显著增加（2.80 vs. 0.83）以及IL-6（0.80 vs. 2.33）和IL-12（0.25 vs. 1.67）的产生减少相结合。我们还表明，表达GILZ的BMSC以有利于Treg细胞的方式呈递抗原。这些结果表明，GILZ在骨髓微环境中介导BMSC和Treg之间的串扰中起关键作用。这些数据以及我们先前的发现，即BMSC中GILZ的过表达拮抗TNF-α引起的炎症反应，表明GILZ在骨免疫细胞通讯和BMSC免疫抑制功能中起重要作用。杨，N.，Baban，B.，伊萨莱斯角M.，施，X。- M.骨髓间充质干细胞和调节性T细胞通过糖皮质激素诱导的亮氨酸拉链/发育内皮基因座-1依赖性机制的相互作用
Bone marrow is a reservoir for regulatory T (Treg) cells, but how Treg cells are regulated in that environment remains poorly understood. We show that expression of glucocorticoid (GC)-induced leucine zipper (GILZ) in bone marrow mesenchymal lineage cells or bone marrow-derived mesenchymal stem cells (BMSCs) increases the production of Treg cells via a mechanism involving the up-regulation of developmental endothelial locus-1 (Del-1), an endogenous leukocyte-endothelial adhesion inhibitor. We found that the expression of Del-1 is increased ∼4-fold in the bone tissues of GILZ transgenic (Tg) mice, and this increase is coupled with a significant increase in the production of IL-10 (2.80 vs. 0.83) and decrease in the production of IL-6 (0.80 vs. 2.33) and IL-12 (0.25 vs. 1.67). We also show that GILZ-expressing BMSCs present antigen in a way that favors Treg cells. These results indicate that GILZ plays a critical role mediating the crosstalk between BMSCs and Treg in the bone marrow microenvironment. These data, together with our previous findings that overexpression of GILZ in BMSCs antagonizes TNF-α-elicited inflammatory responses, suggest that GILZ plays important roles in bone-immune cell communication and BMSC immune suppressive functions.—Yang, N., Baban, B., Isales, C. M., Shi, X.-M. Crosstalk between bone marrow-derived mesenchymal stem cells and regulatory T cells through a glucocorticoid-induced leucine zipper/developmental endothelial locus-1-dependent mechanism.