Different Cell Types Involved in Mediating Concanavalin A Induced Liver Injury: A Comprehensive Overview

Abstract

• Concanavalin A (ConA) induced T cell infiltration and liver injury is a model for acute hepatitis• Important cell types include most white blood cells as well as stromal cells• The ConA model has successfully been used to discover new pathways in hepatitis research• New therapeutic interventions for hepatitis were discovered using the ConA model Introduction Autoimmune hepatitisAutoimmune Hepatitis (AIH) is a chronic liver disease associated with raised plasma liver enzymes like transaminases and the presence of autoantibodies [1,2]. The initial trigger of the disease is unknown but different genetic risk factors have been identified [3,4]. In general, it is believed that multiple perturbations, unidentified environmental factors or drugs and the loss of self-tolerance are needed for the onset and development of AIH. The mechanisms for loss of self-tolerance leading to auto reactivity remain unclear but major contributors such as impaired thymic negative selection and expansion of promiscuous T cell clones are suggested [5]. In AIH, presentation of a self-antigen peptide within a Major Histocompatibility (MHC) II molecule by professional Antigen Presenting Cells (APCs) initiates liver damage. This antigen presentation, in combination with exposure to various cytokines, drives the differentiation of uncommitted CD4 helper T cells and immune reaction that is skewed to a Th1 and Th17 response. However, the Th2 response cannot be ignored because it is important in the production of auto-antibodies, which trigger cellular cytotoxicity and complement activation [6,7]. The current standard treatment of AIH patients consists of non-specific immune suppressing drugs such as corticosteroids in combination with azathioprine, which leads to a decrease in serum aminotransferase levels [8]. AIH animal modelsDespite extensive research on the pathogenesis of AIH, the details of the mechanism remain elusive and the current treatments are non-specific and insufficient. The need for faithful and reliable animal models is therefore high. However, finding a suitable animal model is difficult due to the fact that AIH lacks a precise time of onset, etiological agent and the clinical phenotype is variable. According to Czaja et al., the current AIH models can be divided in two categories: the pathogenic and therapeutic models [1]. Pathogenic models focus on characterization of individual mechanisms contributing to occurrence and severity of the disease. In these perturbed models, individual pathways can be isolated and manipulated in a genetic homogenous background. Next to transgenic models in which target antigens are expressed under the control of liver-specific promoters, several inducible models such as the D Galactosamine (GalN) in com HSOA Journal of Gastroenterology & Hepatology Research Review Article AbstractAutoimmune Hepatitis (AIH) is a chronic liver disease where presentation of a self-antigen peptide by professional antigen presenting cells initiates liver damage and drives the differentiation of uncommitted CD4 helpe...

Negative Influence of Aging on Differentiation and Proliferation of CD8+ T-Cells in Dogs

“…Previous studies used Con A to stimulate PBMCs for evaluating T-cell proliferation [ 25 , 34 ]. However, Con A binds to cell-surface carbohydrates, glycoproteins, and glycolipids, inducing non-specific immune stimulation regardless of species [ 36 ]. Additionally, Con A induces various immune cellular activities, not only in T-cells but also in macrophages and B-cells [ 36 , 37 ].…”

“…However, Con A binds to cell-surface carbohydrates, glycoproteins, and glycolipids, inducing non-specific immune stimulation regardless of species [ 36 ]. Additionally, Con A induces various immune cellular activities, not only in T-cells but also in macrophages and B-cells [ 36 , 37 ]. Furthermore, while Con A is useful for assessing the short-term cell phenotype after addition due to its robust T-cell proliferation activity, its transient effect makes it less suitable for stimulating the large quantities of T-cells required for cell infusion therapies [ 38 ].…”

Stellate cell in hepatic inflammation and acute injury

“…ConA (a mannose/glucose‐binding plant lectin)‐induced liver injury in mice is a widely used experimental model to understand mechanisms of immune cell‐mediated acute hepatitis. ConA administration leads to hepatic recruitment and activation of neutrophils and T cells, and overexpression of cytokines and chemokines (Ballegeer & Libert, 2016; Gantner et al, 1995; Tiegs et al, 1992). ConA‐stimulated neutrophils produce ROS, and recruit CD4 + T lymphocytes; depletion of neutrophils prevents both CD4 + T‐cell recruitment and liver damage (Bonder et al, 2004).…”

Summary of Natural Products Ameliorate Concanavalin A-Induced Liver Injury: Structures, Sources, Pharmacological Effects, and Mechanisms of Action

“…Therefore, Con A-activation of T-cell leads to cytokine-induced hepatic injury, which can be assessed by electron microscopy of the liver and by determining the plasma levels of transaminases [1,3]. This injury is characterized by severe liver inflammation and massive hepatocyte apoptosis/necrosis [4][5][6]. Con A produces oxidative stress by increasing the ROS levels and decreasing antioxidants levels (e.g., glutathione, SH), which leads to an increase in intracellular Ca +2 and accelerates lipid peroxidation that damages the cell membrane and other cellular components [7,8].…”

“…The pathogenesis in this model is unique and it offers several similarities to acute liver diseases seen in human beings such as: acute liver failure, autoimmune hepatitis (AIH), and acute viral hepatitis in which T-cells involvement and immune activation/infiltration were observed. This model selectively details the T-cell functions in inflammatory liver disease [3,6,19]. Therefore, the Con A model is utilized to study the pathogenesis, microscopic morphological changes, and effects of potential treatments for AIH and is recognized as an acceptable and well-characterized model for liver injury mediated by immune responses [20,21].…”