Mesenchymal stem cells: a double-edged sword in regulating immune responses

被引：342

作者：

Li, W. ^{[1
]}

Ren, G. ^{[2
]}

Huang, Y. ^{[1
]}

Su, J. ^{[1
]}

Han, Y. ^{[1
]}

Li, J. ^{[1
]}

Chen, X. ^{[1
]}

Cao, K. ^{[1
]}

Chen, Q. ^{[1
]}

Shou, P. ^{[1
]}

Zhang, L. ^{[2
]}

Yuan, Z-R ^{[2
]}

Roberts, A. L. ^{[2
]}

Shi, S. ^{[3
]}

Le, A. D. ^{[3
]}

Shi, Y. ^{[1
,2
]}

机构：

[1] Shanghai Jiao Tong Univ, Key Lab Stem Cell Biol, Shanghai Inst Biol Sci, Inst Hlth Sci,Chinese Acad Sci,Sch Med, Shanghai 200025, Peoples R China

[2] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Child Hlth Inst New Jersey, New Brunswick, NJ 08901 USA

[3] Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA

来源：

CELL DEATH AND DIFFERENTIATION | 2012年 / 19卷 / 09期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

mesenchymal stem cells; chemokine; immunomodulation; tissue repair; VERSUS-HOST-DISEASE; NITRIC-OXIDE SYNTHASE; II CLINICAL-TRIAL; BONE-MARROW; PHASE-I; IMMUNOSUPPRESSIVE PROPERTIES; MEDIATED IMMUNOSUPPRESSION; LYMPHOCYTE-PROLIFERATION; SYSTEMIC-SCLEROSIS; TRANSPLANTATION;

D O I：

10.1038/cdd.2012.26

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mesenchymal stem cells (MSCs) have been employed successfully to treat various immune disorders in animal models and clinical settings. Our previous studies have shown that MSCs can become highly immunosuppressive upon stimulation by inflammatory cytokines, an effect exerted through the concerted action of chemokines and nitric oxide (NO). Here, we show that MSCs can also enhance immune responses. This immune-promoting effect occurred when proinflammatory cytokines were inadequate to elicit sufficient NO production. When inducible nitric oxide synthase (iNOS) production was inhibited or genetically ablated, MSCs strongly enhance T-cell proliferation in vitro and the delayed-type hypersensitivity response in vivo. Furthermore, iNOS(-/-) MSCs significantly inhibited melanoma growth. It is likely that in the absence of NO, chemokines act to promote immune responses. Indeed, in CCR5(-/-)CXCR3(-/-) mice, the immune-promoting effect of iNOS(-/-) MSCs is greatly diminished. Thus, NO acts as a switch in MSC-mediated immunomodulation. More importantly, the dual effect on immune reactions was also observed in human MSCs, in which indoleamine 2,3-dioxygenase (IDO) acts as a switch. This study provides novel information about the pathophysiological roles of MSCs. Cell Death and Differentiation (2012) 19, 1505-1513; doi:10.1038/cdd.2012.26; published online 16 March 2012

引用

页码：1505 / 1513

页数：9

共 40 条

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