CD80+ dendritic cell derived exosomes inhibit CD8+ T cells through down-regulating NLRP3 expression after liver transplantation

Cui, Bin; Sun, Jie; Li, Shipeng; Zhou, Guang‐Peng; Chen, Xiaojie; Sun, Li‐Ying; Lin, Wei; Zhu, Zhi‐Jun

doi:10.1016/j.intimp.2022.108787

Cited by 8 publications

(7 citation statements)

References 42 publications

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“…Following liver transplantation, a substantial number of immune cells enter the donor liver and interact with immune cells of the graft [22], an effect which leads to increases in immune responses and inflammatory reactions [23]. During this process, the liver will produce and release a large number of cytokines, including chemokines and proinflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

Characterization and Proteomic Analyses of Proinflammatory Cytokines in a Mouse Model of Liver Transplant Rejection

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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Liver transplantation (LT) is an effective strategy for the treatment of end-stage liver disease, but immune rejection remains a significant detriment to the survival and prognosis of these LT patients. While immune rejection is closely related to cytokines, the cytokines investigated within previous studies have been limited and have not included a systematic analysis of proinflammatory cytokines. In the present study, we used a protein chip system and proteomics to detect and analyze serum proinflammatory cytokines and differentially expressed proteins in liver tissue in a mouse model of liver transplantation. In addition, bioinformatics analysis was employed to analyze the proinflammatory cytokines and differential changes in proteins in response to this procedure. With these analyses, we found that serum contents of GC-CSF, CXCL-1, MCP-5, and CXCL-2 were significantly increased after liver transplantation, while IL-5, IL-10, and IL-17 were significantly decreased. Results from Gene Ontology (GO) and KEGG pathway analyses revealed that the cytokine-cytokine receptor, Th1/Th2 cell differentiation, and JAK-STAT signaling pathway were enriched in a network associated with the activation of immune response. Results from our proteomic analysis of liver tissue samples revealed that 470 proteins are increased and 50 decreased, including Anxa1, Anxa2, Acsl4, Sirpa, S100a8, and S100a9. KEGG pathway analysis indicated that the neutrophil extracellular trap formation, NOD-like receptor signaling pathway, and leukocyte transendothelial migration were all associated with liver transplant rejection in these mice. Bioinformatics analysis results demonstrated that CXCL-1/CXCL-2 and S100a8/S100a9 were the genes most closely related to the functions of neutrophils and the mononuclear phagocyte system. These findings provide new insights into some of the critical factors associated with liver transplant rejection and thus offer new targets for the treatment and prevention of this condition.

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Section: Discussionmentioning

confidence: 99%

Characterization and Proteomic Analyses of Proinflammatory Cytokines in a Mouse Model of Liver Transplant Rejection

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Consecutive liver transplant recipients were enrolled in this study between January 2021 and June 2021 at Beijing Friendship Hospital, Capital Medical University. Patients were included if they ( 1 ) received LT for more than one year and ( 2 ) underwent liver biopsy for surveillance biopsies or suspected acute rejection. Patients were excluded if they ( 1 ) underwent chemotherapy ( 2 ), took targeted agents ( 3 ), took immunosuppressive drugs other than tacrolimus, mycophenolate mofetil, or steroids ( 4 ); had any kind of infections ( 5 ), were diagnosed with post-transplant lymphoproliferative disorder ( 6 ), received combined organ transplantation, or ( 7 ) were diagnosed with chronic rejection.…”

Section: Methodsmentioning

confidence: 99%

“…It is well known that immunological rejection is triggered by recognizing allogeneic antigens by antigen-presenting cells (APCs). In the presence of appropriate co-stimulatory molecules and a pro-inflammatory cytokine milieu, activated APCs interact with naïve alloreactive T cells, resulting in the proliferation of alloreactive CD4+ and CD8+ effector T cells and subsequent B-cell proliferation ( 2 , 4 ). Then circulating leukocytes, including activated effector T cells, are recruited into the liver allograft to mediate liver damage ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

“…However, allograft rejection contributing to significantly increased risk of graft failure, all-cause mortality, and graft failure-related death has compromised the short-and long-term prognosis of liver transplant recipients (1). There is mounting evidence that hepatic immune microenvironment, liver-resident and circulating immune cells, and specific molecular pathways are implicated in regulating the balance between transplant immune tolerance and rejection (2)(3)(4). It is well known that immunological rejection is triggered by recognizing allogeneic antigens by antigen-presenting cells (APCs).…”

Section: Introductionmentioning

confidence: 99%

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Potential correlation of allograft infiltrating group 2 innate lymphoid cells with acute rejection after liver transplantation

Sun

Zhou

et al. 2022

Front. Immunol.

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Accumulating evidence indicates the critical roles of group 2 innate lymphoid cells (ILC2s) in immunoregulation. However, the role of ILC2s in acute rejection after liver transplantation (LT) remains elusive. In this study, we analyzed the frequency, counts, and signature cytokines of ILC2s in liver transplant recipients by flow cytometric analysis and multiplex immunofluorescence assay. We also assessed the spatial distribution and correlation between hepatic ILC2s and Treg cells. The changes of ILC2s were dynamically monitored in the mouse LT model. We found that the frequencies of circulating ILC2s were comparable in liver transplant recipients with either rejection or non-rejection compared with the control group. The hepatic ILC2s counts were significantly increased in the rejection group than in the non-rejection and control groups, and a similar trend was observed for Treg cells. In the mouse LT model, allograft infiltrating ILC2s dramatically increased within 14 days post-transplant. The frequency of ILC2s in bone marrow significantly increased at 7 days post-transplant and rapidly decreased at 14 days after LT. Similarly, there was a significant increase in the frequency of splenic ILC2s within two weeks post-transplant. Multiplex immunofluorescence assay showed a close correlation between hepatic ILC2s and Treg cells by analyzing their spatial distribution and distance. In conclusion, the number of allograft infiltrating ILC2s was closely related to rejection after LT. Allograft infiltrating ILC2s may play inhibitory roles in posttransplant immune homeostasis, favoring resolution of liver allograft rejection by interacting with Treg cells or promoting the migration of Tregs cells into the liver allograft.

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“…pointed out that CD80 + DCs played a protective role in liver transplantation because their exosomes inhibited CD8 + T cells by downregulating NLRP3. Further, the population of CD80 + DCs decreased with an increase in CD8 + T cells in the transplanted livers 68 . Therefore, the possible regulation of DCs by MSCs is an active area of research.…”

Section: Dendritic Cellsmentioning

confidence: 99%

Recent advances in the immunomodulation mechanism of mesenchymal stem cell therapy in liver diseases

Liu

Yao

et al. 2023

J of Gastro and Hepatol

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Liver fibrosis, acute liver injury or liver failure, liver tumors, and immune rejection after liver transplantation are common clinical liver diseases. Immune responses are the key to determining the prognosis of liver diseases. Liver transplantation could be the last resort for patients with liver failure. However, the use of liver transplantation is limited because of the scarcity of organ donors, immunological rejection in recipients, and high cost. Mesenchymal stem cells (MSCs) are pluripotent adult stem cells with extensive anti‐inflammatory and immunomodulation effects. MSCs can be effectively used for treating liver diseases but without the limitations that are associated with liver transplantation. Therefore, several clinical trials have utilized MSCs for the treatment of refractory liver diseases and the related mechanism is increasingly being elucidated. We have mainly summarized the recent studies that focus on the immunomodulation mechanism of MSC therapy in liver diseases. Further, we have presented our insights on the prospects of using MSCs in the treatment of liver diseases.

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CD80+ dendritic cell derived exosomes inhibit CD8+ T cells through down-regulating NLRP3 expression after liver transplantation

Cited by 8 publications

References 42 publications

Characterization and Proteomic Analyses of Proinflammatory Cytokines in a Mouse Model of Liver Transplant Rejection

Characterization and Proteomic Analyses of Proinflammatory Cytokines in a Mouse Model of Liver Transplant Rejection

Potential correlation of allograft infiltrating group 2 innate lymphoid cells with acute rejection after liver transplantation

Recent advances in the immunomodulation mechanism of mesenchymal stem cell therapy in liver diseases

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