Administration of Interleukin-35-Conditioned Autologous Tolerogenic Dendritic Cells Prolong Allograft Survival After Heart Transplantation
Background/Aims: IL-35, a powerful suppressor of inflammation and autoimmunity, is primarily secreted by regulatory T cells (Tregs) and can, in turn, promote Treg differentiation. However, the precise effect of IL-35 on dendritic cells (DCs) remains to be clarified. Methods: In this study, we invest...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2018-09-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | https://www.karger.com/Article/FullText/493298 |
| _version_ | 1811341007173713920 |
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| author | Xianglan Liu Yong Sun Yang Zheng Maomao Zhang Xiangyuan Jin Kai Kang Yongshun Wang Shuang Li Hanlu Zhang Qi Zhao Shengnan Zhang Jian Wu Bo Yu |
| author_facet | Xianglan Liu Yong Sun Yang Zheng Maomao Zhang Xiangyuan Jin Kai Kang Yongshun Wang Shuang Li Hanlu Zhang Qi Zhao Shengnan Zhang Jian Wu Bo Yu |
| author_sort | Xianglan Liu |
| collection | DOAJ |
| description | Background/Aims: IL-35, a powerful suppressor of inflammation and autoimmunity, is primarily secreted by regulatory T cells (Tregs) and can, in turn, promote Treg differentiation. However, the precise effect of IL-35 on dendritic cells (DCs) remains to be clarified. Methods: In this study, we investigated the expression of IL-35 in DCs after stimulation with LPS utilizing enzyme linked immunosorbent assay(ELISA), quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting, and the influence of IL-35 on the maturation and function of DCs by mixed lymphocyte reaction assay and flow cytometry. We further examined the regulation of IL-35 in DCs by the microRNA let-7i (let-7i) via transfected with let-7i mimic, inhibitor or suppressor of cytokine signalling 1 (SOCS1) siRNA. IL-35-overexpressing DCs were transfused into BALB/c recipients with C57BL/6 heart transplantations to verify the role of immune tolerance in transplantation. Results: The results showed that IL-35 expression was significantly up-regulated following lipopolysaccharide (LPS)-induced DC maturation. Overexpression of IL-35 suppressed DC maturation, promoted the secretion of anti-inflammatory cytokines, and subsequently affected the balance between Treg and Th17 cells. IL-35 expression in DCs was regulated by let-7i, which targets SOCS1. The transfusion of IL-35-transfected DCs induced Treg generation in mice and prolonged cardiac allograft survival. Conclusion: Our data demonstrated that IL-35 induces tolerogenic DCs which are capable of alleviating allograft rejection. Clinical application of IL-35-treated DCs might be a promising approach for eliciting cardiac allograft immune tolerance. |
| first_indexed | 2024-04-13T18:50:12Z |
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| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-04-13T18:50:12Z |
| publishDate | 2018-09-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
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| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-d4efb29d423c4e77991822aa4fcd9ced2022-12-22T02:34:27ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-09-014931221123710.1159/000493298493298Administration of Interleukin-35-Conditioned Autologous Tolerogenic Dendritic Cells Prolong Allograft Survival After Heart TransplantationXianglan LiuYong SunYang ZhengMaomao ZhangXiangyuan JinKai KangYongshun WangShuang LiHanlu ZhangQi ZhaoShengnan ZhangJian WuBo YuBackground/Aims: IL-35, a powerful suppressor of inflammation and autoimmunity, is primarily secreted by regulatory T cells (Tregs) and can, in turn, promote Treg differentiation. However, the precise effect of IL-35 on dendritic cells (DCs) remains to be clarified. Methods: In this study, we investigated the expression of IL-35 in DCs after stimulation with LPS utilizing enzyme linked immunosorbent assay(ELISA), quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting, and the influence of IL-35 on the maturation and function of DCs by mixed lymphocyte reaction assay and flow cytometry. We further examined the regulation of IL-35 in DCs by the microRNA let-7i (let-7i) via transfected with let-7i mimic, inhibitor or suppressor of cytokine signalling 1 (SOCS1) siRNA. IL-35-overexpressing DCs were transfused into BALB/c recipients with C57BL/6 heart transplantations to verify the role of immune tolerance in transplantation. Results: The results showed that IL-35 expression was significantly up-regulated following lipopolysaccharide (LPS)-induced DC maturation. Overexpression of IL-35 suppressed DC maturation, promoted the secretion of anti-inflammatory cytokines, and subsequently affected the balance between Treg and Th17 cells. IL-35 expression in DCs was regulated by let-7i, which targets SOCS1. The transfusion of IL-35-transfected DCs induced Treg generation in mice and prolonged cardiac allograft survival. Conclusion: Our data demonstrated that IL-35 induces tolerogenic DCs which are capable of alleviating allograft rejection. Clinical application of IL-35-treated DCs might be a promising approach for eliciting cardiac allograft immune tolerance.https://www.karger.com/Article/FullText/493298Interleukin-35Dendritic cellsRegulatory T cellsLet-7iTransplant immunity |
| spellingShingle | Xianglan Liu Yong Sun Yang Zheng Maomao Zhang Xiangyuan Jin Kai Kang Yongshun Wang Shuang Li Hanlu Zhang Qi Zhao Shengnan Zhang Jian Wu Bo Yu Administration of Interleukin-35-Conditioned Autologous Tolerogenic Dendritic Cells Prolong Allograft Survival After Heart Transplantation Cellular Physiology and Biochemistry Interleukin-35 Dendritic cells Regulatory T cells Let-7i Transplant immunity |
| title | Administration of Interleukin-35-Conditioned Autologous Tolerogenic Dendritic Cells Prolong Allograft Survival After Heart Transplantation |
| title_full | Administration of Interleukin-35-Conditioned Autologous Tolerogenic Dendritic Cells Prolong Allograft Survival After Heart Transplantation |
| title_fullStr | Administration of Interleukin-35-Conditioned Autologous Tolerogenic Dendritic Cells Prolong Allograft Survival After Heart Transplantation |
| title_full_unstemmed | Administration of Interleukin-35-Conditioned Autologous Tolerogenic Dendritic Cells Prolong Allograft Survival After Heart Transplantation |
| title_short | Administration of Interleukin-35-Conditioned Autologous Tolerogenic Dendritic Cells Prolong Allograft Survival After Heart Transplantation |
| title_sort | administration of interleukin 35 conditioned autologous tolerogenic dendritic cells prolong allograft survival after heart transplantation |
| topic | Interleukin-35 Dendritic cells Regulatory T cells Let-7i Transplant immunity |
| url | https://www.karger.com/Article/FullText/493298 |
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