Naringenin Impedes the Differentiation of Mouse Hematopoietic Stem Cells Derived from Bone Marrow into Mature Dendritic Cells, thereby Prolonging Allograft Survival
Background: The use of immature dendritic cells (imDCs) to induce donor-specific immunotolerance following in vivo stimulation is limited by their low rate of induction and their tendency to undergo maturation. We derived imDCs from bone marrow hematopoietic stem cells (HSCs-imDCs). We then tested t...
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| Format: | Article |
| Language: | English |
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IMR Press
2023-05-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/28/5/10.31083/j.fbl2805091 |
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| author | Puxun Tian Xiaoyan Huang Kun Zhu Zhankui Jin Yan Li Bingxuan Zheng Xiangrong Zhao Yangmeng Feng Qing Feng Dongliang Li Jiaojiao Wang Cuixiang Xu |
| author_facet | Puxun Tian Xiaoyan Huang Kun Zhu Zhankui Jin Yan Li Bingxuan Zheng Xiangrong Zhao Yangmeng Feng Qing Feng Dongliang Li Jiaojiao Wang Cuixiang Xu |
| author_sort | Puxun Tian |
| collection | DOAJ |
| description | Background: The use of immature dendritic cells (imDCs) to induce donor-specific immunotolerance following in vivo stimulation is limited by their low rate of induction and their tendency to undergo maturation. We derived imDCs from bone marrow hematopoietic stem cells (HSCs-imDCs). We then tested the ability of naringenin (Nar) to impede the maturation of HSCs-imDCs for inducing transplantation immune tolerance. Methods: HSCs derived from bone marrow were collected and induced to differentiate into imDCs by treating with Nar (Nar-HSCs-imDCs). Flow cytometry was used to evaluate DC surface markers, apoptosis, and endocytic ability. The ability of DCs to influence the in vitro proliferation of T cells and of regulatory T cells (Tregs) was analyzed by mixed lymphocyte reaction assays. Enzyme-linked immunoassays were used to quantify cytokine levels in supernatants from co-cultured DCs and Tregs, as well as in the serum of experimental animals. The level of immunotolerance induced by Nar-HSCs-imDCs was evaluated by skin grafting in recipient Balb/c mice, while the Kaplan-Meier method was used to statistically evaluate graft survival. Results: Compared with HSC-imDCs, Nar-HSCs-imDCs showed higher expression of cluster of differentiation 11c (CD11c), but lower expression levels of CD80, CD86, and major histocompatibility complex class II. Nar-HSCs-imDCs also showed stronger inhibition of T cells and higher Treg cell proliferation. Interleukin 2 (IL-2) and interferon gamma levels were downregulated in Nar-HSCs-imDCs, whereas IL-4, IL-10, and transforming growth factor beta levels were upregulated. The rate of apoptosis and endocytic capacity of Nar-HSCs-DCs increased significantly after treatment with lipopolysaccharide. HSCs-imDCs or Nar-HSCs-imDCs were injected into Balb/c mice via the tail vein 7 days before skin grafting. Significantly reduced donor-specific CD4+ T cells and induced proliferation of CD4+CD25+FoxP3+ Treg cells were observed in the spleen of mice from the Nar-HSCs-imDCs group, especially at a dose of 106 Nar-HSCs-imDCs. The latter group also showed significantly prolonged survival of skin grafts. Conclusions: Nar-HSCs-imDCs markedly improved the acceptance of organ allografts, offering a potentially new strategy for inducing immune tolerance in transplantation. |
| first_indexed | 2024-03-13T08:06:59Z |
| format | Article |
| id | doaj.art-13cbe786e3884f8eac5bd688e2728432 |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-03-13T08:06:59Z |
| publishDate | 2023-05-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-13cbe786e3884f8eac5bd688e27284322023-06-01T02:53:04ZengIMR PressFrontiers in Bioscience-Landmark2768-67012023-05-012859110.31083/j.fbl2805091S2768-6701(23)00847-XNaringenin Impedes the Differentiation of Mouse Hematopoietic Stem Cells Derived from Bone Marrow into Mature Dendritic Cells, thereby Prolonging Allograft SurvivalPuxun Tian0Xiaoyan Huang1Kun Zhu2Zhankui Jin3Yan Li4Bingxuan Zheng5Xiangrong Zhao6Yangmeng Feng7Qing Feng8Dongliang Li9Jiaojiao Wang10Cuixiang Xu11Department of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, ChinaDepartment of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, ChinaDepartment of Pathology, The First Affiliated Hospital of Xi’an Jiaotong University, 710061 Xi'an, Shaanxi, ChinaDepartment of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, ChinaDepartment of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, ChinaDepartment of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, ChinaDepartment of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, ChinaDepartment of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, ChinaDepartment of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, ChinaDepartment of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, ChinaDepartment of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, ChinaDepartment of Kidney Transplantation, Hospital of Nephropathy, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, ChinaBackground: The use of immature dendritic cells (imDCs) to induce donor-specific immunotolerance following in vivo stimulation is limited by their low rate of induction and their tendency to undergo maturation. We derived imDCs from bone marrow hematopoietic stem cells (HSCs-imDCs). We then tested the ability of naringenin (Nar) to impede the maturation of HSCs-imDCs for inducing transplantation immune tolerance. Methods: HSCs derived from bone marrow were collected and induced to differentiate into imDCs by treating with Nar (Nar-HSCs-imDCs). Flow cytometry was used to evaluate DC surface markers, apoptosis, and endocytic ability. The ability of DCs to influence the in vitro proliferation of T cells and of regulatory T cells (Tregs) was analyzed by mixed lymphocyte reaction assays. Enzyme-linked immunoassays were used to quantify cytokine levels in supernatants from co-cultured DCs and Tregs, as well as in the serum of experimental animals. The level of immunotolerance induced by Nar-HSCs-imDCs was evaluated by skin grafting in recipient Balb/c mice, while the Kaplan-Meier method was used to statistically evaluate graft survival. Results: Compared with HSC-imDCs, Nar-HSCs-imDCs showed higher expression of cluster of differentiation 11c (CD11c), but lower expression levels of CD80, CD86, and major histocompatibility complex class II. Nar-HSCs-imDCs also showed stronger inhibition of T cells and higher Treg cell proliferation. Interleukin 2 (IL-2) and interferon gamma levels were downregulated in Nar-HSCs-imDCs, whereas IL-4, IL-10, and transforming growth factor beta levels were upregulated. The rate of apoptosis and endocytic capacity of Nar-HSCs-DCs increased significantly after treatment with lipopolysaccharide. HSCs-imDCs or Nar-HSCs-imDCs were injected into Balb/c mice via the tail vein 7 days before skin grafting. Significantly reduced donor-specific CD4+ T cells and induced proliferation of CD4+CD25+FoxP3+ Treg cells were observed in the spleen of mice from the Nar-HSCs-imDCs group, especially at a dose of 106 Nar-HSCs-imDCs. The latter group also showed significantly prolonged survival of skin grafts. Conclusions: Nar-HSCs-imDCs markedly improved the acceptance of organ allografts, offering a potentially new strategy for inducing immune tolerance in transplantation.https://www.imrpress.com/journal/FBL/28/5/10.31083/j.fbl2805091naringeninhematopoietic stem cellsimmature dendritic cellsimmune toleranceskin graft |
| spellingShingle | Puxun Tian Xiaoyan Huang Kun Zhu Zhankui Jin Yan Li Bingxuan Zheng Xiangrong Zhao Yangmeng Feng Qing Feng Dongliang Li Jiaojiao Wang Cuixiang Xu Naringenin Impedes the Differentiation of Mouse Hematopoietic Stem Cells Derived from Bone Marrow into Mature Dendritic Cells, thereby Prolonging Allograft Survival Frontiers in Bioscience-Landmark naringenin hematopoietic stem cells immature dendritic cells immune tolerance skin graft |
| title | Naringenin Impedes the Differentiation of Mouse Hematopoietic Stem Cells Derived from Bone Marrow into Mature Dendritic Cells, thereby Prolonging Allograft Survival |
| title_full | Naringenin Impedes the Differentiation of Mouse Hematopoietic Stem Cells Derived from Bone Marrow into Mature Dendritic Cells, thereby Prolonging Allograft Survival |
| title_fullStr | Naringenin Impedes the Differentiation of Mouse Hematopoietic Stem Cells Derived from Bone Marrow into Mature Dendritic Cells, thereby Prolonging Allograft Survival |
| title_full_unstemmed | Naringenin Impedes the Differentiation of Mouse Hematopoietic Stem Cells Derived from Bone Marrow into Mature Dendritic Cells, thereby Prolonging Allograft Survival |
| title_short | Naringenin Impedes the Differentiation of Mouse Hematopoietic Stem Cells Derived from Bone Marrow into Mature Dendritic Cells, thereby Prolonging Allograft Survival |
| title_sort | naringenin impedes the differentiation of mouse hematopoietic stem cells derived from bone marrow into mature dendritic cells thereby prolonging allograft survival |
| topic | naringenin hematopoietic stem cells immature dendritic cells immune tolerance skin graft |
| url | https://www.imrpress.com/journal/FBL/28/5/10.31083/j.fbl2805091 |
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