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 | |
| State | Published - Nov 1 2014 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Cite this
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
}
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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84932176456&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84932176456&partnerID=8YFLogxK
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 -