Interleukin-17 enhances immunosuppression by mesenchymal stem cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-07-18

AUTHORS

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

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. More... »

PAGES

1758-1768

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/cdd.2014.85

    DOI

    http://dx.doi.org/10.1038/cdd.2014.85

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1019044633

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25034782


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