Autophagic activation of IRF‐1 aggravates hepatic ischemia–reperfusion injury via JNK signaling

Li, Shipeng; He, Jun; Xu, Hongwei; Yang, Jiaxing; Luo, Yutian; Song, Wenya; Qiao, Bingbing; Zhang, Haiming

doi:10.1002/mco2.58

Cited by 12 publications

(7 citation statements)

References 29 publications

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“…Following incubation in 3% H 2 O 2 for 10 min, antibodies anti-CD4, CD8, CD11b, CD14, and CD15 were added and incubated at 4°C for overnight. The specimens were incubated with secondary antibodies at 37°Cfor 1 h, followed by diaminobenzidine staining ( 26 ).…”

Section: Methodsmentioning

confidence: 99%

Landscape of Immune Cells Heterogeneity in Liver Transplantation by Single-Cell RNA Sequencing Analysis

et al. 2022

Front. Immunol.

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Rejection is still a critical barrier to the long-term survival of graft after liver transplantation, requiring clinicians to unveil the underlying mechanism of liver transplant rejection. The cellular diversity and the interplay between immune cells in the liver graft microenvironment remain unclear. Herein, we performed single-cell RNA sequencing analysis to delineate the landscape of immune cells heterogeneity in liver transplantation. T cells, NK cells, B cells, and myeloid cell subsets in human liver and blood were enriched to characterize their tissue distribution, gene expression, and functional modules. The proportion of CCR6+CD4+ T cells increased within an allograft, suggesting that there are more memory CD4+ T cells after transplantation, in parallel with exhausted CTLA4+CD8+ T and actively proliferating MKI67+CD8+ T cells increased significantly, where they manifested heterogeneity, distinct function, and homeostatic proliferation. Remarkably, the changes of CD1c+ DC, CADM+ DC, MDSC, and FOLR3+ Kupffer cells increase significantly, but the proportion of CD163+ Kupffer, APOE+ Kupffer, and GZMA+ Kupffer decreased. Furthermore, we identified LDLR as a novel marker of activated MDSC to prevent liver transplant rejection. Intriguingly, a subset of CD4+CD8+FOXP3+ T cells included in CTLA4+CD8+ T cells was first detected in human liver transplantation. Furthermore, intercellular communication and gene regulatory analysis implicated the LDLR+ MDSC and CTLA4+CD8+ T cells interact through TIGIT-NECTIN2 signaling pathway. Taken together, these findings have gained novel mechanistic insights for understanding the immune landscape in liver transplantation, and it outlines the characteristics of immune cells and provides potential therapeutic targets in liver transplant rejection.

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Section: Methodsmentioning

confidence: 99%

Landscape of Immune Cells Heterogeneity in Liver Transplantation by Single-Cell RNA Sequencing Analysis

et al. 2022

Front. Immunol.

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“…Hepatic IRI, represents a significant risk factor affecting the prognosis of hepatectomy or liver transplantation (25). The mechanisms of hepatic IRI are complex, involving oxidative stress, apoptosis, autophagy, pyroptosis and immune factors (26,27), and it is also certain that resident liver macrophages, play an important role in this liver injury process (28)(29)(30). According to the different functions exerted by macrophages, they can be divided into M1 macrophages that promote or M2 macrophages that inhibit inflammation (31).…”

Section: Discussionmentioning

confidence: 99%

ILC2s expanded by exogenous IL-33 regulate CD45+CD11b+F4/80high macrophage polarization to alleviate hepatic ischemia-reperfusion injury

Zhang

Chen

et al. 2022

Front. Immunol.

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Hepatic ischemia-reperfusion injury (IRI) is an adverse consequence of hepatectomy or liver transplantation. Recently, immune mechanisms involved in hepatic IRI have attracted increased attention of investigators working in this area. In specific, group 2 innate lymphoid cells (ILC2s), have been strongly implicated in mediating type 2 inflammation. However, their immune mechanisms as involved with hepatic IRI remain unclear. Here, we reported that the population of ILC2s is increased with the development of hepatic IRI as shown in a mouse model in initial stage. Moreover, M2 type CD45+CD11b+F4/80high macrophages increased and reached maximal levels at 24 h followed by a significant elevation in IL-4 levels. We injected exogenous IL-33 into the tail vein of mice as a mean to stimulate ILC2s production. This stimulation of ILC2s resulted in a protective effect upon hepatic IRI along with an increase in M2 type CD45+CD11b+F4/80high macrophages. In contrast, depletion of ILC2s as achieved with use of an anti-CD90.2 antibody substantially abolished this protective effect of exogenous IL-33 and M2 type CD45+CD11b+F4/80high macrophage polarization in hepatic IRI. Therefore, this exogenous IL-33 induced potentiation of ILC2s appears to regulate the polarization of CD45+CD11b+F4/80high macrophages to alleviate IRI. Such findings provide the foundation for the development of new targets and strategies in the treatment of hepatic IRI.

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“…Blood samples from all mice were collected, and serum was obtained following centrifugation. Serum AST and ALT levels were determined using the mouse transaminase test kit (Shanghai Yaji Biotechnology, China) [20].…”

Section: Serum Ast and Alt Determinationsmentioning

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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Autophagic activation of IRF‐1 aggravates hepatic ischemia–reperfusion injury via JNK signaling

Cited by 12 publications

References 29 publications

Landscape of Immune Cells Heterogeneity in Liver Transplantation by Single-Cell RNA Sequencing Analysis

Landscape of Immune Cells Heterogeneity in Liver Transplantation by Single-Cell RNA Sequencing Analysis

ILC2s expanded by exogenous IL-33 regulate CD45+CD11b+F4/80high macrophage polarization to alleviate hepatic ischemia-reperfusion injury

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

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