Pathogenesis of Concanavalin A induced autoimmune hepatitis in mice

Hao, Jianheng; Sun, Weili; Xu, Huichao

doi:10.1016/j.intimp.2021.108411

Cited by 32 publications

(31 citation statements)

References 54 publications

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“…Since macrophages could be activated 1 h of ConA injection ( 28 ). Then, we gated the F4/80 + cell population among CD45 + ( Figure 5A ).…”

Section: Resultsmentioning

confidence: 99%

“…In 1992, Tiegs et al established an acute immune hepatitis model by intravenously injecting ConA ( 30 ). ConA in one of the lectins mostly binds to the hepatocyte membrane to induce liver injury via T cells and macrophages ( 28 ). The mechanisms of ConA mouse model have been studied for several years, and the main standpoints were focused on active T cells, NKT, and macrophages ( 28 , 31 , 32 ).…”

Section: Discussionmentioning

confidence: 99%

“…ConA in one of the lectins mostly binds to the hepatocyte membrane to induce liver injury via T cells and macrophages ( 28 ). The mechanisms of ConA mouse model have been studied for several years, and the main standpoints were focused on active T cells, NKT, and macrophages ( 28 , 31 , 32 ). MenSCs could be an effective treatment for cholestatic liver injury by regulating β-catenin expression ( 24 ) and antifibrotic capacity in chronic liver diseases ( 17 ).…”

Section: Discussionmentioning

confidence: 99%

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Comprehensive immune cell analysis of human menstrual-blood-derived stem cells therapy to concanavalin A hepatitis

Zhang

Fan²,

Liu³

et al. 2022

Front. Immunol.

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Autoimmune hepatitis is an autoimmune disease with increasing occurrence worldwide. The most common and convenient mouse model is the concanavalin A (ConA) mouse model. Human menstrual-blood-derived stem cells (MenSCs) have shown great potential as a type of mesenchymal stem cell for treating various diseases. Time-of-flight mass cytometry was performed in phosphate-buffered saline control (NC) group and ConA injection with or without MenSCs treatment groups, and conventional flow cytometry was used for further validation. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and H&E staining depicted that MenSCs treatment could significantly alleviate ConA-induced hepatitis. The t-distributed stochastic neighbor embedding (t-SNE) analysis of nine liver samples displayed favorable cell clustering, and the NC group was significantly different from the other two groups. The proportions of CD69+ T cells, NKT cells, and PD-L1+ macrophages were notably increased by ConA injection, while MenSCs could decrease ConA-induced macrophage percentage and M1 polarization in the liver tissue. The analysis of proinflammatory factors carried out by cytometric bead array demonstrated that tumor necrosis factor alpha (TNF-α), interleukin (IL)-17A, IL-12p70, IL-6, IL-2, IL-1b, and interferon gamma (IFN-γ) were upregulated after ConA injection and then rapidly decreased at 12 h. MenSCs also played an important role in downregulating these cytokines. Here, we described the comprehensive changes in leukocytes in the liver tissue of ConA-induced hepatitis at 12 h after ConA injection and found that MenSCs rescued ConA-induced hepatitis mostly by inhibiting macrophages and M1 polarization in mouse liver.

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“…Since macrophages could be activated 1 h of ConA injection ( 28 ). Then, we gated the F4/80 + cell population among CD45 + ( Figure 5A ).…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Comprehensive immune cell analysis of human menstrual-blood-derived stem cells therapy to concanavalin A hepatitis

Zhang

Fan²,

Liu³

et al. 2022

Front. Immunol.

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“…In Con A induced liver injury, the binding of Con A to the Kupffer cells (KCs) results in the activation of KCs, which release inflammatory mediators. The MHC class II on KCs modified by Con A could be recognized by T cell receptors on T cells, and make T cells activated, thereby enhancing the secretion of inflammatory factors, and ultimately leading to liver cell apoptosis ( 10 ). Based on our results that corilagin inhibited the activation of macrophages, and it also influenced the activation of T cells and NKT cells, suggesting that corilagin could disrupt the interactions between immune cells in liver injury.…”

Section: Discussionmentioning

confidence: 99%

“…As T lymphocyte mitogen, Con A primarily leads to recruitment and activation of T cells after intravenous injection, which induces hepatotoxic cytokines such as IFN-γ, TNF-α, IL-4, IL-5, and eventually lead to liver injury ( 7 , 10 ). NKT cells, which account for a large proportion in mice liver, can aggravate inflammation and liver injury by the apoptosis related factor ligand (FasL), perforin, granzyme and inflammatory cytokines ( 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

Corilagin Ameliorates Con A-Induced Hepatic Injury by Restricting M1 Macrophage Polarization

et al. 2022

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Immune-mediated hepatic injury plays a key role in the initiation and pathogenesis of diverse liver diseases. However, treatment choice for immune-mediated hepatic injury remains limited. Corilagin, a natural ellagitannin extracted from various traditional Chinese medicines, has been demonstrated to exhibit multiple pharmacological activities, such as anti-inflammatory, anti-tumor, and hepatoprotective properties. The present study aimed to investigate the effects of corilagin on immune-mediated hepatic injury using a murine model of concanavalin A (Con A)-induced hepatitis, which is well-characterized to study acute immune-mediated hepatitis. Herein, mice were administered corilagin (25 mg/kg) intraperitoneally twice at 12 h intervals, and 1 h later, the mice were challenged with Con A (20 mg/kg body weight); serum and liver samples were collected after 12 h. The results showed that corilagin significantly increased the survival of mice and reduced serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels. In addition, corilagin markedly improved histopathological damage, hepatocyte apoptosis, and oxidative stress in the liver. The activation of M1 macrophages in the hepatic mononuclear cells was also significantly reduced compared with that in the control group. The expression of M1 macrophage-associated proinflammatory cytokines and genes, including interleukin (IL)-6, IL-12, and inducible nitric oxide synthase (iNOS), was also decreased after corilagin treatment. Finally, the results demonstrated that corilagin regulated macrophage polarization by modulating the mitogen-activated protein kinases (MAPK), nuclear factor (NF)-κB, and interferon regulatory factor (IRF) signaling pathways. Thus, the findings indicate that corilagin protects mice from Con A-induced immune-mediated hepatic injury by limiting M1 macrophage activation via the MAPK, NF-κB, and IRF signaling pathways, suggesting corilagin as a possible treatment choice for immune-mediated hepatic injury.

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Concanavalin‐A‐Induced Acute Liver Injury in Mice

Nabekura,

Matsuo,

Shibuya

2024

Current Protocols

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Acute liver injury is a life‐threatening disease. Although immune responses are involved in the development and exacerbation of acute liver injury, the cellular and molecular mechanisms are not fully understood. Intravenous administration of the plant lectin concanavalin A (ConA) is widely used as a model of acute liver injury. ConA triggers T cell activation and cytokine production by crosslinking glycoproteins, including the T cell receptor, leading to the infiltration of myeloid cells into the liver and the subsequent amplification of inflammation in the liver. Thus, the pathogenesis of ConA‐induced acute liver injury is considered a model of immune‐mediated acute liver injury or autoimmune hepatitis in humans. However, the severity of the liver injury and the analyses of immune cells and non‐hematopoietic cells in the liver following ConA injection are significantly influenced by the experimental conditions. This article outlines protocols for ConA‐induced acute liver injury in mice and evaluation methods for liver injury, immune cells, and non‐hematopoietic cells in the liver. © 2024 Wiley Periodicals LLC.Basic Protocol 1: Induction of acute liver injury by ConA injectionBasic Protocol 2: Evaluation of inflammatory cytokines in mouse plasmaBasic Protocol 3: Preparation of liver sections and histological analysis of liver injuryBasic Protocol 4: Preparation of liver immune cellsBasic Protocol 5: Preparation of hepatocytes, endothelial cells, and hepatic stellate cellsBasic Protocol 6: Flow cytometry of immune and non‐hematopoietic liver cellsBasic Protocol 7: Flow cytometric sorting of endothelial cells and hepatic stellate cellsBasic Protocol 8: Quantitative reverse transcription polymerase chain reaction

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Pathogenesis of Concanavalin A induced autoimmune hepatitis in mice

Cited by 32 publications

References 54 publications

Comprehensive immune cell analysis of human menstrual-blood-derived stem cells therapy to concanavalin A hepatitis

Comprehensive immune cell analysis of human menstrual-blood-derived stem cells therapy to concanavalin A hepatitis

Corilagin Ameliorates Con A-Induced Hepatic Injury by Restricting M1 Macrophage Polarization

Concanavalin‐A‐Induced Acute Liver Injury in Mice

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