Activation of cellular death programs associated with immunosenescence-like 
phenotype in TPPII knockout mice

Huai, Jisen; Firat, Elke; Nil, Ahmed; Million, Daniele; Gaedicke, Simone; Kanzler, Benoit; Freudenberg, Marina; van Endert, Peter; Kohler, Gabriele; Pahl, Heike L.; Aichele, Peter; Eichmann, Klaus; Niedermann, Gabriele

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Activation of cellular death programs associated with immunosenescence-like phenotype in TPPII knockout mice

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Firat, Elke
Georges Köhler Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Nil, Ahmed
Emeritus Group: Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191216

Million, Daniele
Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191062

Gaedicke, Simone
Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191144

Kanzler, Benoit
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191059

Freudenberg, Marina
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191039

Eichmann, Klaus
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191247

Niedermann, Gabriele
Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Huai, J., Firat, E., Nil, A., Million, D., Gaedicke, S., Kanzler, B., et al. (2008). Activation of cellular death programs associated with immunosenescence-like phenotype in TPPII knockout mice. Proceedings of the National Academy of Sciences of the United States of America, 105, 5177-5182.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002B-90A3-8

Abstract

The giant cytosolic protease tripeptidyl peptidase II (TPPII) has been implicated in the regulation of proliferation and survival of malignant cells, particularly lymphoma cells. To address its functions in normal cellular and systemic physiology we have generated TPPII-deficient mice. TPPII deficiency activates cell type-specific death programs, including proliferative apoptosis in several T lineage subsets and premature cellular senescence in fibroblasts and CD8⁺ T cells. This coincides with up-regulation of p53 and dysregulation of NF-κB. Prominent degenerative alterations at the organismic level were a decreased lifespan and symptoms characteristic of immunohematopoietic senescence. These symptoms include accelerated thymic involution, lymphopenia, impaired proliferative T cell responses, extramedullary hematopoiesis, and inflammation. Thus, TPPII is important for maintaining normal cellular and systemic physiology, which may be relevant for potential therapeutic applications of TPPII inhibitors.