Liver Injury Model in Mice Induced by a Cellular Immunologic Mechanism—Delayed-Type Hypersensitivity-Induced Liver Injury to Picryl Chloride and Phenotype of Effector Cell

Xu, Qiang; Wang, Rong; Jiang, Jieyun; Wu, Feihua; Lu, Jianhua; Tan, Poi Kiang; Xu, Li

doi:10.1006/cimm.1996.0005

Cited by 20 publications

(24 citation statements)

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“…The key role of the CD4 ϩ T lymphocytes that mainly constitute liver-infiltrating leukocytes in this model has been reported in our previous papers. 5,6,12) Against this model, SiNi-San showed remarkable alleviation when administered during either the induction or effector phase, as did cyclophosphamide (Fig. 2).…”

Section: Discussionmentioning

confidence: 86%

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Alleviating Effects of Si-Ni-San, a Traditional Chinese Prescription, on Experimental Liver Injury and Its Mechanisms

Jiang

Zhou

2003

Biological & Pharmaceutical Bulletin

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Section: Discussionmentioning

confidence: 86%

“…In histopathological examinations, the main changes in liver injury were inflammatory infiltration and hepatocellular coagulation necrosis, as reported previously. 5,6,[12][13][14] These changes were remarkably reduced in most of the mice by Si-Ni-San and cyclophosphamide (data not shown).…”

Section: Fig 1 Effect Of Si-ni-san On CCL 4 -Induced Hepatocyte Dammentioning

confidence: 99%

Alleviating Effects of Si-Ni-San, a Traditional Chinese Prescription, on Experimental Liver Injury and Its Mechanisms

Jiang

Zhou

2003

Biological & Pharmaceutical Bulletin

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“…The injection of Con A in rodents rapidly induces polyclonal T cell activation, which leads to clinical and histological symptoms of acute hepatitis (6,7). The liver injury of T cell-mediated immunity in human acute hepatitis mimicked in mice by a delayed-type hypersensitivity to picryl chloride (PIH) (8)(9)(10)(11)(12). This hepatic injury is mediated by CD4 + T cells.…”

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confidence: 99%

Targeting S1P1 Receptor Protects against Murine Immunological Hepatic Injury through Myeloid-Derived Suppressor Cells

Liu

Wang

et al. 2014

The Journal of Immunology

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Although FTY720 may alter migration and homing of lymphocytes via sphingosine-1-phosphate (S1P) receptors, our recent studies indicated that FTY720 directly controls the differentiation of Th1 cells to regulatory T cells (Tregs) by targeting S1P1. However, the pharmacological function of FTY720 in immunological hepatic injury remains unknown. In this study, the role and regulatory signaling pathway of S1P receptor were investigated using a pharmacological approach in immune-mediated hepatic injury (IMH). In the context of IMH, FTY720 significantly ameliorated mortality and hepatic pathology. In FTY720-treated mice, recruited CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs) mediate protection against IMH and are functional suppressive immune modulators that result in fewer IFN-γ–producing Th1 cells and more Foxp3+ Tregs. In agreement, FTY720-treated MDSCs promote the reciprocal differentiation between Th1 cells and Tregs in vitro and in vivo. Mechanistically, FTY720 treatment induced inducible NO synthase expression and NO production in MDSCs. Pharmacologic inhibition of inducible NO synthase completely eliminates MDSC suppressive function and eradicates their inducible effects on T cell differentiation. Finally, the mTOR inhibitor, rapamycin, photocopies the effects of FTY720 on MDSCs, implicating mTOR as a downstream effector of S1P1 signaling. This study identifies MDSCs as an essential component that provides protection against IMH following FTY720 or rapamycin treatment, validating the S1P1–mTOR signaling axis as a potential therapeutic target in hepatic injury.

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“…To mimic the cellular immunological pathogenesis of human hepatitis in animals, we have previously reported a novel liver injury model induced in mice by DTH reaction to picryl chloride (PCl-DTH), and demonstrated the key role of CD4+ T cells in the injury induction [12, 13]. Interestingly, this injury induced locally in liver was not limited to the PCl injection site but involved wide histological changes around the site in most mice and sometimes even throughout the liver [13].…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, this injury induced locally in liver was not limited to the PCl injection site but involved wide histological changes around the site in most mice and sometimes even throughout the liver [13]. Moreover, this one-shot DTH reaction in the mouse liver caused a sustained liver injury for a period of several months.…”

Section: Introductionmentioning

confidence: 99%

Role of CD4+ and CD8+ T cells in Regulating the Chronic Development of Liver Injury Induced by Delayed-Type Hypersensitivity to Picryl Chloride

Wu²,

Jiang³

et al. 1998

Int Arch Allergy Immunol

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In this study we first investigated the cellular immune responses in mice with chronic liver injury induced by delayed-type hypersensitivity to picryl chloride (PCl). A continuous reduction, after week 3 of liver injury, was observed in the level of PCl-induced contact sensitivity but not in sheep red blood cell-induced footpad reaction, suggesting the presence of PCl-specific suppression. When spleen cells from mice whose liver had been injured for 1 week were systemically transferred into syngeneic recipients with the liver injury, the elevation in serum lactic dehydrogenase and the decrease in alkaline phosphatase and albumin levels in recipient mice were significantly exacerbated. However, when the liver damage in the donor mouse was allowed to proceed for 3, 5 or 7 weeks, biochemical changes in recipients were reduced to near normal levels. A flow-cytometric assay demonstrated that the number of CD4+ T cells in both spleen cells and liver nonparenchymal cells decreased dramatically during the late phase of liver injury, while CD8+ counts did not. These findings suggest that CD4+ and CD8+ T lymphocytes may contribute to the positive and negative regulation, respectively, of the early and late phases in the chronic development of liver injury.

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Liver Injury Model in Mice Induced by a Cellular Immunologic Mechanism—Delayed-Type Hypersensitivity-Induced Liver Injury to Picryl Chloride and Phenotype of Effector Cell

Cited by 20 publications

References 0 publications

Alleviating Effects of Si-Ni-San, a Traditional Chinese Prescription, on Experimental Liver Injury and Its Mechanisms

Alleviating Effects of Si-Ni-San, a Traditional Chinese Prescription, on Experimental Liver Injury and Its Mechanisms

Targeting S1P1 Receptor Protects against Murine Immunological Hepatic Injury through Myeloid-Derived Suppressor Cells

Role of CD4+ and CD8+ T cells in Regulating the Chronic Development of Liver Injury Induced by Delayed-Type Hypersensitivity to Picryl Chloride

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