TY - JOUR
T1 - Interleukin-17 enhances immunosuppression by mesenchymal stem cells
AU - Han, X.
AU - Yang, Q.
AU - Lin, L.
AU - Xu, C.
AU - Zheng, C.
AU - Chen, X.
AU - Han, Y.
AU - Li, M.
AU - Cao, W.
AU - Cao, K.
AU - Chen, Q.
AU - Xu, G.
AU - Zhang, Y.
AU - Zhang, J.
AU - Schneider, R. J.
AU - Qian, Y.
AU - Wang, Y.
AU - Brewer, G.
AU - Shi, Y.
N1 - Funding Information:
Acknowledgements. This work was supported by grants from the Ministry of Science and Technology of China (2010CB945600 and 2011DFA30630), Scientific Innovation Project of the Chinese Academy of Science (XDA 01040107 and XDA 01040110), the Programs of National Natural Science of China (81330046, 81273316), the External Cooperation Program of BIC, Chinese Academy of Sciences (GJHZ201307), Shanghai Municipal Key Projects of Basic Research (12JC1409200), Shanghai Municipal Natural Science Foundation (12ZR1452600), the Knowledge Innovation Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (2012KIP202).
Publisher Copyright:
© 2014 Macmillan Publishers Limited All rights reserved.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - IL-17 is one of the most potent and most actively investigated proinflammatory cytokines. In this study, we examined the effect of IL-17 on mesenchymal stem cells (MSCs) under the influence of inflammatory cytokines. Ironically, IL-17 dramatically enhanced the immunosuppressive effect of MSCs induced by IFNγ and TNFα, revealing a novel role of IL-17 in immunosuppression. Interestingly, we found that this action of IL-17 was dependent on the promoted expression of a key immune suppressive molecule, inducible nitric oxide synthase (iNOS), in MSCs. In a concanavalin A (ConA)-induced hepatitis mouse model, we found that IL-17 also enhanced the in vivo immunosuppressive effect of MSCs in an iNOS-dependent manner. Moreover, this promoting effect of IL-17 was found to be exerted through enhancing mRNA stability by modulating the protein level of ARE/poly(U)-binding/degradation factor 1 (AUF1), a well-known factor that promotes mRNA decay. In auf1-/-MSCs, IFNγ and TNFα could induce maximal immunosuppressive effect, both in vitro and in vivo, without the need for IL-17. Thus, our studies demonstrated that in the presence of MSCs, IL-17 promotes immunosuppression.
AB - IL-17 is one of the most potent and most actively investigated proinflammatory cytokines. In this study, we examined the effect of IL-17 on mesenchymal stem cells (MSCs) under the influence of inflammatory cytokines. Ironically, IL-17 dramatically enhanced the immunosuppressive effect of MSCs induced by IFNγ and TNFα, revealing a novel role of IL-17 in immunosuppression. Interestingly, we found that this action of IL-17 was dependent on the promoted expression of a key immune suppressive molecule, inducible nitric oxide synthase (iNOS), in MSCs. In a concanavalin A (ConA)-induced hepatitis mouse model, we found that IL-17 also enhanced the in vivo immunosuppressive effect of MSCs in an iNOS-dependent manner. Moreover, this promoting effect of IL-17 was found to be exerted through enhancing mRNA stability by modulating the protein level of ARE/poly(U)-binding/degradation factor 1 (AUF1), a well-known factor that promotes mRNA decay. In auf1-/-MSCs, IFNγ and TNFα could induce maximal immunosuppressive effect, both in vitro and in vivo, without the need for IL-17. Thus, our studies demonstrated that in the presence of MSCs, IL-17 promotes immunosuppression.
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U2 - 10.1038/cdd.2014.85
DO - 10.1038/cdd.2014.85
M3 - Article
C2 - 25034782
AN - SCOPUS:84932176456
VL - 21
SP - 1758
EP - 1768
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
SN - 1350-9047
IS - 11
ER -