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 journalArticle

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 languageEnglish (US)
Pages (from-to)1758-1768
Number of pages11
JournalCell Death and Differentiation
Volume21
Issue number11
DOIs
StatePublished - Nov 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    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