Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide

被引：1768

作者：

Ren, Guangwen ^{[1
]}

Zhang, Liying ^{[1
]}

Zhao, Xin ^{[1
]}

Xu, Guangwu ^{[1
]}

Zhang, Yingyu ^{[1
]}

Roberts, Arthur I. ^{[1
]}

Zhao, Robert Chunhua ^{[2
,3
,4
]}

Shi, Yufang ^{[1
]}

机构：

[1] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet Microbiol & Immunol, Piscataway, NJ 08854 USA

[2] Chinese Acad Med Sci, Inst Basic Med Sci, Ctr Excellence Tissue Engn, Beijing 100005, Peoples R China

[3] Chinese Acad Med Sci, Sch Bas Med, Beijing 100005, Peoples R China

[4] Peking Union Med Coll, Beijing 100005, Peoples R China

来源：

CELL STEM CELL | 2008年 / 2卷 / 02期

关键词：

D O I：

10.1016/j.stem.2007.11.014

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Mesenchymal stem cells (MSCs) can become potently immunosuppressive through unknown mechanisms. We found that the immunosuppressive function of MSCs is elicited by IFN gamma and the concomitant presence of any of three other proinflammatory cytokines, TNF alpha, IL-1 alpha, or IL-beta. These cytokine combinations provoke the expression of high levels of several chemokines and inducible nitric oxide synthase (iNOS) by MSCs. Chemokines drive T cell migration into proximity with MSCs, where T cell responsiveness is suppressed by nitric oxide (NO). This cytokine-induced immunosuppression was absent in MSCs derived from iNOS(-/-) or IFN gamma R1(-/-) mice. Blockade of chemokine receptors also abolished the immunosuppression. Administration of wild-type MSCs, but not IFNyR1(-/-) or iNOS(-/-) MSCs, prevented graft-versus-host disease in mice, an effect reversed by anti-IFN gamma or iNOS inhibitors. Wild-type MSCs also inhibited delayed-type hypersensitivity, while iNOS(-/-) MSCs aggravated it. Therefore, proinflammatory cytokines are required to induce immunosuppression by MSCs through the concerted action of chemokines and NO.

引用

页码：141 / 150

页数：10

共 56 条

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