title: Interleukin-17 enhances immunosuppression by mesenchymal stem cells.
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.
authors.affiliation: 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.
authors.forename: X
authors.initials: X
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: L
authors.initials: L
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: C
authors.initials: C
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: C
authors.initials: C
authors.lastname: Zheng
authors.affiliation: 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.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Y
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ, USA.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.affiliation: 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.
authors.forename: W
authors.initials: W
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: K
authors.initials: K
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Child Health Institute of New Jersey, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: G
authors.initials: G
authors.lastname: Xu
authors.affiliation: Child Health Institute of New Jersey, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Child Health Institute of New Jersey, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, New York University School of Medicine, New York, NY, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Schneider
authors.affiliation: 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.
authors.forename: Y
authors.initials: Y
authors.lastname: Qian
authors.affiliation: 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.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ, USA.
authors.forename: G
authors.initials: G
authors.lastname: Brewer
authors.affiliation: 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 [2] Child Health Institute of New Jersey, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D015870:Gene Expression; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism*; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000494:pharmacology; D020381:Interleukin-17 / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D020871:RNA Stability; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000630987:Hnrpd protein, mouse; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II