The study of the mechanisms of immunomodulatory function of mesenchymal stem cells.

间充质干细胞免疫调节功能机制的研究。

基本信息

批准号：
22790918
负责人：
TATARA Raine
金额：
$ 2.16万
依托单位：
Jichi Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2011
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790918/
关键词：
間葉系幹細胞同種骨髄移植移植片対宿主病(GVHD)Th17 制御性T細胞 GVHD Th17細胞

项目摘要

Mesenchymal stem cells(MSCs) possess an immunomodulatory function and show promise as a cell therapy for graft-versus-host disease(GVHD). But the molecular mechanism(s) underlying immunomodulation by MSCs has not been fully established. Th17 is a recently recognized differentiation category, in which CD4 cells produce IL-17, and regulatory T cells(Treg) are another newly recognized differentiation category, in which CD4 T cells have high levels of Foxp3 expression and suppress T cell proliferation. These two differentiations are thought in a reciprocal relationship. While the role of Th17 in GVHD is still controversial, some investigators reported that Th17 has aggravating effects on GVHD. Treg has been reported to suppress GVHD in a mouse model. To elucidate the molecular mechanism(s) of the immunomodulatory function of MSCs, we herein sought to identify the effects of MSCs on these relatively new T cell differentiations. MSCs inhibited Th17 differentiation even in conditions in which T cell growth was not completely inhibited. Interestingly, an inhibitor of prostaglandin production, indomethacin, and an inhibitor of IDO, 1-methyltryptophan(1-MT), partially restored Th17 differentiation. These results suggest that PGE2 and depletion of tryptophan mediate inhibitory effects of MSCs on Th17.On the other hand, Treg differentiation was not significantly enhanced by MSCs. The mechanisms by which IDO and PGE2 regulate these differentiations are unknown.

间充质干细胞（MSC）具有免疫调节功能，有望成为移植物抗宿主病（GVHD）的细胞疗法。但间充质干细胞免疫调节的分子机制尚未完全确定。 Th17是最近被认可的分化类别，其中CD4细胞产生IL-17，调节性T细胞（Treg）是另一个新被认可的分化类别，其中CD4 T细胞具有高水平的Foxp3表达并抑制T细胞增殖。这两种区别被认为是相互关系的。虽然Th17在GVHD中的作用仍存在争议，但一些研究人员报道Th17对GVHD有加重作用。据报道，Treg 可在小鼠模型中抑制 GVHD。为了阐明 MSC 免疫调节功能的分子机制，我们在此试图确定 MSC 对这些相对较新的 T 细胞分化的影响。即使在 T 细胞生长未被完全抑制的条件下，MSC 也会抑制 Th17 分化。有趣的是，前列腺素生成抑制剂吲哚美辛和 IDO 抑制剂 1-甲基色氨酸 (1-MT) 可以部分恢复 Th17 分化。这些结果表明PGE2和色氨酸的消耗介导MSCs对Th17的抑制作用。另一方面，MSCs并没有显着增强Treg分化。 IDO 和 PGE2 调节这些分化的机制尚不清楚。