Study of cellular inetractions in experimental autoimmune hepatitis in mice.

Mori, Yoshio; Ogawa, Makoto; Mori, Teruo; Ueda, Shiro; Yoshida, Hiromichi; Kato, Isao; Iesato, K; Wakashin, Y; Wakashin, M; Okuda, Kunio

doi:10.2957/kanzo.28.283

Cited by 11 publications

(13 citation statements)

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“…3). Thus, although the autoAg recognized by mouse sera were not identified, the autoimmune response shown in this work was somewhat comparable to that described in the various animal models of autoimmune hepatitis (AIH) reported in the literature [15,[24][25][26][27].…”

Section: Discussionsupporting

confidence: 86%

“…Most animal models to simulate AIH are based on rather complex ways of disease induction, such as xenoimmunization with human antigens [24,25], the use of adenovirus vectors [15,27] or transgenic mice [26]. Here we show that a simple and common phenomenon, i.e., a viral infection followed by a toxic liver injury, may induce certain signs of AIH disease.…”

Section: Discussionmentioning

confidence: 76%

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The autoimmune response induced by mouse hepatitis virus A59 is expanded by a hepatotoxic agent

Aparicio

Vega

Loureiro

et al. 2009

International Immunopharmacology

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Mouse hepatitis virus strain A59 (MHV-A59) triggers various pathologies in several mouse strains, including hypergammaglobulinaemia, hepatitis and thymus involution. We reported previously the presence of autoantibodies (autoAb) to liver and kidney fumarylacetoacetate hydrolase (FAH) in sera from mice infected with MHV-A59. Long-term MHV-infected mice represented a good model of non-pathogenic autoimmune response since the animals were apparently healthy in spite of the presence of autoAb. The aim of this work was to see whether a severe liver injury, which releases endogenous adjuvants, i.e. danger signals, could elicit a broader spectrum of autoAb and perhaps signs of autoimmune hepatitis. Carbon tetrachloride (CCl(4)) was injected into mice 30 days after MHV infection, and serum was assayed for autoAb and total IgG 20 days later. The association of MHV infection with the toxic effects of CCl(4) resulted in hypergammaglobulinaemia and the production of autoAb to various liver and kidney proteins. Histological examination of liver samples showed tissue damages but without significant differences between the animals submitted to MHV+CCl(4) and controls, which were either infected by MHV without CCl(4), or poisoned by CCl(4) in the absence of MHV infection. Those results show that liver injury after viral infection may lead to the spreading of the immune response and to an increase of serum IgG, suggesting that the procedure used herein could simulate the onset of autoimmune hepatitis.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 76%

The autoimmune response induced by mouse hepatitis virus A59 is expanded by a hepatotoxic agent

Aparicio

Vega

Loureiro

et al. 2009

International Immunopharmacology

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“…Evidence for the loss of central immune tolerance in AIH comes from murine studies [23][24][25] and inducing non-specific T-cell activation in mice has been shown to result in T-cell mediated liver injury [26] . Evidence for the importance of mTECs in impaired central tolerance leading to AIH has also been shown experimentally [27] , and is further corroborated by the description of a few families with AIRE deficiency -this gene plays a part in controlling antigen presentation in mTECs [28] , and affected individuals suffer with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, a syndrome that includes a 20% prevalence of AIH [29] .…”

Section: Immunologymentioning

confidence: 99%

The Pathogenesis of Autoimmune Liver Disease

Arndtz

Hirschfield

2016

Dig Dis

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Background: Autoimmune liver disease (AILD) encompasses 3 main distinct clinical diseases: autoimmune hepatitis, primary biliary cholangitis (formally known as cirrhosis, PBC) and primary sclerosing cholangitis (PSC). These conditions are an important, yet under-appreciated cause of patient morbidity and mortality with ongoing unmet needs for further research and clinical advances. Key Messages: There is observational evidence for genetic predisposition, with all 3 conditions being more common in first degree relatives. AILD is associated with the presence of auto-antibodies and higher risks of other non-hepatic auto-immune conditions. Genetic risk association studies have identified HLA and non-HLA risk loci for the development of disease, with some HLA loci providing prognostic information. This re-enforces the concept that genetic predisposition to autoimmunity is important, likely in the context of environmental exposures. Such environmental triggers are unclear but relevant risks include smoking, drug and xenobiotic exposure as well as the complexities of the microbiome. There is evidence for a loss of immune tolerance to self-antigens playing a part in the development of these conditions. In particular the IL-2 and IL-12 regulatory pathways have been implicated in pre-disposing to an unopposed inflammatory response within the liver. Main immunological themes revolve around loss of immune tolerance leading to T-cell mediated injury, imbalance in the regulation of immune cells and defective immune response to foreign antigens. For PBC and PSC, there is then the added complexity of the consequences of cholestasis on hepato-biliary injury, immune regulation and liver fibrosis. Conclusions: Whilst specific disease causes and triggers are still lacking, AILD arises on the background of collective genetic and environmental risk, leading to chronic and abnormal hepato-biliary immune responses. Effective and more rational therapy will ultimately be developed when the multiple pathways to liver injury are better understood.

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“…Mori et al [18] changed the experimental set-up and induced AIH by syngeneic S-100 SN (supernatant of liver homogenate centrifuged with 100 k g ). It was demonstrated that the inbred C57Bl/6J strain was much more susceptible to experimental autoimmune hepatitis (EAH) than Balb/c and C3H/He mice.…”

Section: Models Of Experimental Aih Immunization Strategiesmentioning

confidence: 99%

Mouse Models for Experimental Autoimmune Hepatitis: Limits and Chances

Hardtke‐Wolenski

Jaeckel²

2010

Dig Dis

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The difficulty in studying human autoimmune hepatitis (AIH) is usually the late time-point of diagnosis which is followed by long-standing immunosuppression and the fact that human immune responses can usually only be studied in peripheral blood. Therefore, animal models with defined onset of AIH and, ideally, a positive impact of standard therapeutic interventions are key to understanding the disease and its pathophysiology, and providing a platform for new therapy options or better prevention. For over a century, the lack of a reliable model with a chronic immune response against hepatocytes has been a key problem in AIH research. Initial attempts to break tolerance against liver tissue resulted in mild and transient hepatitis. Many transgenic models demonstrated different aspects of liver-specific immune regulation. The fate of liver-specific T cells is under intense research and many mechanisms have demonstrated ignorance, anergy, deletion or TCR downregulation. Furthermore, these studies defined a role of professional antigen-presenting cells and especially of liver sinusoidal cells. Other models have shown the mechanism of T cell activation in liver and the interaction of adaptive and innate immune cells. Most recently, some approaches have been made to establish models of chronic AIH resembling human disease. These attempts might open new research chances to study AIH onset and its pathophysiology, and they might result in new options for therapy and prevention research.

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Study of cellular inetractions in experimental autoimmune hepatitis in mice.

Cited by 11 publications

References 0 publications

The autoimmune response induced by mouse hepatitis virus A59 is expanded by a hepatotoxic agent

The autoimmune response induced by mouse hepatitis virus A59 is expanded by a hepatotoxic agent

The Pathogenesis of Autoimmune Liver Disease

Mouse Models for Experimental Autoimmune Hepatitis: Limits and Chances

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