Parenchymal, but not leukocyte, TNF receptor 2 mediates T cell-dependent hepatitis in mice.

Jens Schümann; Katrin Mühlen; Alexandra K Kiemer; Angelika M Vollmar; Gisa Tiegs

Parenchymal, but not leukocyte, TNF receptor 2 mediates T cell-dependent hepatitis in mice.

Standard

Parenchymal, but not leukocyte, TNF receptor 2 mediates T cell-dependent hepatitis in mice. / Schümann, Jens; Mühlen, Katrin; Kiemer, Alexandra K; Vollmar, Angelika M; Tiegs, Gisa.

In: J IMMUNOL, Vol. 170, No. 4, 4, 2003, p. 2129-2137.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schümann, J, Mühlen, K, Kiemer, AK, Vollmar, AM & Tiegs, G 2003, 'Parenchymal, but not leukocyte, TNF receptor 2 mediates T cell-dependent hepatitis in mice.', J IMMUNOL, vol. 170, no. 4, 4, pp. 2129-2137. <http://www.ncbi.nlm.nih.gov/pubmed/12574385?dopt=Citation>

APA

Schümann, J., Mühlen, K., Kiemer, A. K., Vollmar, A. M., & Tiegs, G. (2003). Parenchymal, but not leukocyte, TNF receptor 2 mediates T cell-dependent hepatitis in mice. J IMMUNOL, 170(4), 2129-2137. [4]. http://www.ncbi.nlm.nih.gov/pubmed/12574385?dopt=Citation

Vancouver

Schümann J, Mühlen K, Kiemer AK, Vollmar AM, Tiegs G. Parenchymal, but not leukocyte, TNF receptor 2 mediates T cell-dependent hepatitis in mice. J IMMUNOL. 2003;170(4):2129-2137. 4.

Bibtex

@article{a677611f165c481ab6109e9578c86d5a,

title = "Parenchymal, but not leukocyte, TNF receptor 2 mediates T cell-dependent hepatitis in mice.",

abstract = "TNF-alpha is a central mediator of T cell activation-induced hepatitis in mice, e.g., induced by Pseudomonas exotoxin A (PEA). In this in vivo mouse model of T cell-dependent hepatitis, liver injury depends on both TNFRs. Whereas TNFR1 can directly mediate hepatocyte death, the in vivo functions of TNFR2 in pathophysiology remained unclear. TNFR2 has been implicated in deleterious leukocyte activation in a transgenic mouse model and in enhancement of TNFR1-mediated cell death in cell lines. In this study, we clarify the role of hepatocyte- vs leukocyte-expressed TNFR2 in T cell-dependent liver injury in vivo, using the PEA-induced hepatitis model. Several types of TNFR2-expressing leukocytes, especially neutrophils and NK cells, accumulated within the liver throughout the pathogenic process. Surprisingly, only parenchymal TNFR2 expression, but not the TNFR2 expression on leukocytes, contributed to PEA-induced hepatitis, as shown by analysis of wild-type --> tnfr2 degrees and the reciprocal mouse bone marrow chimeras. Furthermore, PEA induced NF-kappaB activation and cytokine production in the livers of both wild-type and tnfr2 degrees mice, whereas only primary mouse hepatocytes from wild-type, but not from tnfr2 degrees, mice were susceptible to cell death induced by a combination of agonistic anti-TNFR1 and anti-TNFR2 Abs. Our results suggest that parenchymal, but not leukocyte, TNFR2 mediates T cell-dependent hepatitis in vivo. The activation of leukocytes does not appear to be disturbed by the absence of TNFR2.",

keywords = "Animals, Male, Cells, Cultured, Mice, Mice, Inbred C57BL, Mice, Transgenic, Bone Marrow Transplantation, NF-kappa B/metabolism, Injections, Intravenous, Cell Death/immunology, Antigens, CD/biosynthesis/blood/*physiology/radiation effects, Bacterial Proteins/toxicity, Bone Marrow Cells/immunology/radiation effects, Drug-Induced Liver Injury/*immunology/*pathology/therapy, Hepatocytes/*immunology/*metabolism, Interleukin-6/biosynthesis, Kupffer Cells/immunology/metabolism, Leukocyte Transfusion, Leukocytes/*immunology/*metabolism/radiation effects, Radiation Chimera, Receptors, Tumor Necrosis Factor/biosynthesis/blood/*physiology/radiation effects, Receptors, Tumor Necrosis Factor, Type II, Signal Transduction/immunology, T-Lymphocyte Subsets/*immunology, Tumor Necrosis Factor-alpha/biosynthesis, Animals, Male, Cells, Cultured, Mice, Mice, Inbred C57BL, Mice, Transgenic, Bone Marrow Transplantation, NF-kappa B/metabolism, Injections, Intravenous, Cell Death/immunology, Antigens, CD/biosynthesis/blood/*physiology/radiation effects, Bacterial Proteins/toxicity, Bone Marrow Cells/immunology/radiation effects, Drug-Induced Liver Injury/*immunology/*pathology/therapy, Hepatocytes/*immunology/*metabolism, Interleukin-6/biosynthesis, Kupffer Cells/immunology/metabolism, Leukocyte Transfusion, Leukocytes/*immunology/*metabolism/radiation effects, Radiation Chimera, Receptors, Tumor Necrosis Factor/biosynthesis/blood/*physiology/radiation effects, Receptors, Tumor Necrosis Factor, Type II, Signal Transduction/immunology, T-Lymphocyte Subsets/*immunology, Tumor Necrosis Factor-alpha/biosynthesis",

author = "Jens Sch{\"u}mann and Katrin M{\"u}hlen and Kiemer, {Alexandra K} and Vollmar, {Angelika M} and Gisa Tiegs",

year = "2003",

language = "English",

volume = "170",

pages = "2129--2137",

journal = "J IMMUNOL",

issn = "0022-1767",

publisher = "American Association of Immunologists",

number = "4",

}

RIS

TY - JOUR

T1 - Parenchymal, but not leukocyte, TNF receptor 2 mediates T cell-dependent hepatitis in mice.

AU - Schümann, Jens

AU - Mühlen, Katrin

AU - Kiemer, Alexandra K

AU - Vollmar, Angelika M

AU - Tiegs, Gisa

PY - 2003

Y1 - 2003

N2 - TNF-alpha is a central mediator of T cell activation-induced hepatitis in mice, e.g., induced by Pseudomonas exotoxin A (PEA). In this in vivo mouse model of T cell-dependent hepatitis, liver injury depends on both TNFRs. Whereas TNFR1 can directly mediate hepatocyte death, the in vivo functions of TNFR2 in pathophysiology remained unclear. TNFR2 has been implicated in deleterious leukocyte activation in a transgenic mouse model and in enhancement of TNFR1-mediated cell death in cell lines. In this study, we clarify the role of hepatocyte- vs leukocyte-expressed TNFR2 in T cell-dependent liver injury in vivo, using the PEA-induced hepatitis model. Several types of TNFR2-expressing leukocytes, especially neutrophils and NK cells, accumulated within the liver throughout the pathogenic process. Surprisingly, only parenchymal TNFR2 expression, but not the TNFR2 expression on leukocytes, contributed to PEA-induced hepatitis, as shown by analysis of wild-type --> tnfr2 degrees and the reciprocal mouse bone marrow chimeras. Furthermore, PEA induced NF-kappaB activation and cytokine production in the livers of both wild-type and tnfr2 degrees mice, whereas only primary mouse hepatocytes from wild-type, but not from tnfr2 degrees, mice were susceptible to cell death induced by a combination of agonistic anti-TNFR1 and anti-TNFR2 Abs. Our results suggest that parenchymal, but not leukocyte, TNFR2 mediates T cell-dependent hepatitis in vivo. The activation of leukocytes does not appear to be disturbed by the absence of TNFR2.

AB - TNF-alpha is a central mediator of T cell activation-induced hepatitis in mice, e.g., induced by Pseudomonas exotoxin A (PEA). In this in vivo mouse model of T cell-dependent hepatitis, liver injury depends on both TNFRs. Whereas TNFR1 can directly mediate hepatocyte death, the in vivo functions of TNFR2 in pathophysiology remained unclear. TNFR2 has been implicated in deleterious leukocyte activation in a transgenic mouse model and in enhancement of TNFR1-mediated cell death in cell lines. In this study, we clarify the role of hepatocyte- vs leukocyte-expressed TNFR2 in T cell-dependent liver injury in vivo, using the PEA-induced hepatitis model. Several types of TNFR2-expressing leukocytes, especially neutrophils and NK cells, accumulated within the liver throughout the pathogenic process. Surprisingly, only parenchymal TNFR2 expression, but not the TNFR2 expression on leukocytes, contributed to PEA-induced hepatitis, as shown by analysis of wild-type --> tnfr2 degrees and the reciprocal mouse bone marrow chimeras. Furthermore, PEA induced NF-kappaB activation and cytokine production in the livers of both wild-type and tnfr2 degrees mice, whereas only primary mouse hepatocytes from wild-type, but not from tnfr2 degrees, mice were susceptible to cell death induced by a combination of agonistic anti-TNFR1 and anti-TNFR2 Abs. Our results suggest that parenchymal, but not leukocyte, TNFR2 mediates T cell-dependent hepatitis in vivo. The activation of leukocytes does not appear to be disturbed by the absence of TNFR2.

KW - Animals

KW - Male

KW - Cells, Cultured

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Bone Marrow Transplantation

KW - NF-kappa B/metabolism

KW - Injections, Intravenous

KW - Cell Death/immunology

KW - Antigens, CD/biosynthesis/blood/physiology/radiation effects

KW - Bacterial Proteins/toxicity

KW - Bone Marrow Cells/immunology/radiation effects

KW - Drug-Induced Liver Injury/immunology/pathology/therapy

KW - Hepatocytes/immunology/metabolism

KW - Interleukin-6/biosynthesis

KW - Kupffer Cells/immunology/metabolism

KW - Leukocyte Transfusion

KW - Leukocytes/immunology/metabolism/radiation effects

KW - Radiation Chimera

KW - Receptors, Tumor Necrosis Factor/biosynthesis/blood/physiology/radiation effects

KW - Receptors, Tumor Necrosis Factor, Type II

KW - Signal Transduction/immunology

KW - T-Lymphocyte Subsets/immunology

KW - Tumor Necrosis Factor-alpha/biosynthesis