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T Cell–specific Ablation of Fas Leads to Fas Ligand–mediated Lymphocyte Depletion and Inflammatory Pulmonary Fibrosis
To study the role of Fas–Fas ligand (FasL) interaction-mediated apoptosis in lymphocyte homeostasis, we generated a mutant fas allele allowing conditional inactivation of the fas gene through Cre-mediated recombination. Experiments in which Fas was ablated in T cells, B cells, T and B cells, or in a...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2004
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211818/ https://www.ncbi.nlm.nih.gov/pubmed/15148335 http://dx.doi.org/10.1084/jem.20032196 |
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author | Hao, Zhenyue Hampel, Brigitte Yagita, Hideo Rajewsky, Klaus |
author_facet | Hao, Zhenyue Hampel, Brigitte Yagita, Hideo Rajewsky, Klaus |
author_sort | Hao, Zhenyue |
collection | PubMed |
description | To study the role of Fas–Fas ligand (FasL) interaction-mediated apoptosis in lymphocyte homeostasis, we generated a mutant fas allele allowing conditional inactivation of the fas gene through Cre-mediated recombination. Experiments in which Fas was ablated in T cells, B cells, T and B cells, or in a more generalized manner demonstrated that the development of lymphoproliferative disease as seen in Fas-deficient mice requires Fas ablation in lymphoid and nonlymphoid tissues. Selective inactivation of Fas in T cells led to a severe lymphopenia over time, accompanied by up-regulation of FasL on activated T cells and apoptosis of peripheral lymphocytes. In addition, the mutant animals developed a fatal wasting syndrome caused by massive leukocyte infiltration in the lungs together with increased inflammatory cytokine production and pulmonary fibrosis. Inhibition of Fas–FasL interaction in vivo completely prevented the loss of lymphocytes and initial lymphocyte infiltration in the lungs. Thus, FasL-mediated interaction of activated, Fas-deficient T cells with Fas-expressing cells in their environment leads to break down of lymphocyte homeostasis and development of a lung disease strikingly resembling idiopathic pulmonary fibrosis in humans, a common and severe disease for which the mutant mice may serve as a first animal model. |
format | Text |
id | pubmed-2211818 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22118182008-03-11 T Cell–specific Ablation of Fas Leads to Fas Ligand–mediated Lymphocyte Depletion and Inflammatory Pulmonary Fibrosis Hao, Zhenyue Hampel, Brigitte Yagita, Hideo Rajewsky, Klaus J Exp Med Article To study the role of Fas–Fas ligand (FasL) interaction-mediated apoptosis in lymphocyte homeostasis, we generated a mutant fas allele allowing conditional inactivation of the fas gene through Cre-mediated recombination. Experiments in which Fas was ablated in T cells, B cells, T and B cells, or in a more generalized manner demonstrated that the development of lymphoproliferative disease as seen in Fas-deficient mice requires Fas ablation in lymphoid and nonlymphoid tissues. Selective inactivation of Fas in T cells led to a severe lymphopenia over time, accompanied by up-regulation of FasL on activated T cells and apoptosis of peripheral lymphocytes. In addition, the mutant animals developed a fatal wasting syndrome caused by massive leukocyte infiltration in the lungs together with increased inflammatory cytokine production and pulmonary fibrosis. Inhibition of Fas–FasL interaction in vivo completely prevented the loss of lymphocytes and initial lymphocyte infiltration in the lungs. Thus, FasL-mediated interaction of activated, Fas-deficient T cells with Fas-expressing cells in their environment leads to break down of lymphocyte homeostasis and development of a lung disease strikingly resembling idiopathic pulmonary fibrosis in humans, a common and severe disease for which the mutant mice may serve as a first animal model. The Rockefeller University Press 2004-05-17 /pmc/articles/PMC2211818/ /pubmed/15148335 http://dx.doi.org/10.1084/jem.20032196 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Hao, Zhenyue Hampel, Brigitte Yagita, Hideo Rajewsky, Klaus T Cell–specific Ablation of Fas Leads to Fas Ligand–mediated Lymphocyte Depletion and Inflammatory Pulmonary Fibrosis |
title | T Cell–specific Ablation of Fas Leads to Fas Ligand–mediated Lymphocyte Depletion and Inflammatory Pulmonary Fibrosis |
title_full | T Cell–specific Ablation of Fas Leads to Fas Ligand–mediated Lymphocyte Depletion and Inflammatory Pulmonary Fibrosis |
title_fullStr | T Cell–specific Ablation of Fas Leads to Fas Ligand–mediated Lymphocyte Depletion and Inflammatory Pulmonary Fibrosis |
title_full_unstemmed | T Cell–specific Ablation of Fas Leads to Fas Ligand–mediated Lymphocyte Depletion and Inflammatory Pulmonary Fibrosis |
title_short | T Cell–specific Ablation of Fas Leads to Fas Ligand–mediated Lymphocyte Depletion and Inflammatory Pulmonary Fibrosis |
title_sort | t cell–specific ablation of fas leads to fas ligand–mediated lymphocyte depletion and inflammatory pulmonary fibrosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211818/ https://www.ncbi.nlm.nih.gov/pubmed/15148335 http://dx.doi.org/10.1084/jem.20032196 |
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