Interleukin-17 enhances immunosuppression by mesenchymal stem cells

X. Han; Q. Yang; L. Lin; C. Xu; C. Zheng; X. Chen; Y. Han; M. Li; W. Cao; K. Cao; Q. Chen; G. Xu; Y. Zhang; J. Zhang; R. J. Schneider; Y. Qian; Y. Wang; G. Brewer; Y. Shi

doi:10.1038/cdd.2014.85

Interleukin-17 enhances immunosuppression by mesenchymal stem cells

X. Han, Q. Yang, L. Lin, C. Xu, C. Zheng, X. Chen, Y. Han, M. Li, W. Cao, K. Cao, Q. Chen, G. Xu, Y. Zhang, J. Zhang, R. J. Schneider, Y. Qian, Y. Wang, G. Brewer, Y. Shi

Research output: Contribution to journal › Article

63 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1758-1768
Number of pages	11
Journal	Cell Death and Differentiation
Volume	21
Issue number	11
DOIs	https://doi.org/10.1038/cdd.2014.85
State	Published - Nov 1 2014
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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Han, X., Yang, Q., Lin, L., Xu, C., Zheng, C., Chen, X., Han, Y., Li, M., Cao, W., Cao, K., Chen, Q., Xu, G., Zhang, Y., Zhang, J., Schneider, R. J., Qian, Y., Wang, Y., Brewer, G., & Shi, Y. (2014). Interleukin-17 enhances immunosuppression by mesenchymal stem cells. Cell Death and Differentiation, 21(11), 1758-1768. https://doi.org/10.1038/cdd.2014.85

Interleukin-17 enhances immunosuppression by mesenchymal stem cells. / Han, X.; Yang, Q.; Lin, L.; Xu, C.; Zheng, C.; Chen, X.; Han, Y.; Li, M.; Cao, W.; Cao, K.; Chen, Q.; Xu, G.; Zhang, Y.; Zhang, J.; Schneider, R. J.; Qian, Y.; Wang, Y.; Brewer, G.; Shi, Y.

In: Cell Death and Differentiation, Vol. 21, No. 11, 01.11.2014, p. 1758-1768.

Research output: Contribution to journal › Article

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abstract = "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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