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

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Interleukin-17 enhances immunosuppression by mesenchymal stem cells

Journal article

Open access

Peer reviewed

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, …

Cell death and differentiation, Vol.21(11), pp.1758-1768

11/2014

DOI: https://doi.org/10.1038/cdd.2014.85

PMCID: PMC4211372

PMID: 25034782

Abstract

Animals

Heterogeneous-Nuclear Ribonucleoprotein D - metabolism

Immune Tolerance

Interferon-gamma - pharmacology

Interleukin-17 - physiology

Mesenchymal Stromal Cells - immunology

Mesenchymal Stromal Cells - metabolism

Mice

Nitric Oxide Synthase Type II - metabolism

RNA Stability

Tumor Necrosis Factor-alpha - pharmacology

Gene Expression

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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Title: Interleukin-17 enhances immunosuppression by mesenchymal stem cells
Creators: X Han - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China
Q Yang - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China
L Lin - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China
C Xu - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China
C Zheng - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China
X Chen - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China
Y Han - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China
M Li - Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ, USA
W Cao - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China
K Cao - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China
Q Chen - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China
G Xu - Child Health Institute of New Jersey, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
Y Zhang - Child Health Institute of New Jersey, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
J Zhang - Child Health Institute of New Jersey, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
R J Schneider - Department of Microbiology, New York University School of Medicine, New York, NY, USA
Y Qian - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China
Y Wang - Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China
G Brewer - Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ, USA
Y Shi - 1] Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China Child Health Institute of New Jersey, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
Publication Details: Cell death and differentiation, Vol.21(11), pp.1758-1768
Date published: 11/2014
Academic Unit: Biochemistry and Molecular Biology (RWJMS)
Language: English
Resource Type: Journal article
Identifiers: 991031665457304646