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Lack of Foxp3 function and expression in the thymic epithelium
Foxp3 is essential for the commitment of differentiating thymocytes to the regulatory CD4(+) T (T reg) cell lineage. In humans and mice with a genetic Foxp3 deficiency, absence of this critical T reg cell population was suggested to be responsible for the severe autoimmune lesions. Recently, it has...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2137899/ https://www.ncbi.nlm.nih.gov/pubmed/17353370 http://dx.doi.org/10.1084/jem.20062465 |
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author | Liston, Adrian Farr, Andrew G. Chen, Zhibin Benoist, Christophe Mathis, Diane Manley, Nancy R. Rudensky, Alexander Y. |
author_facet | Liston, Adrian Farr, Andrew G. Chen, Zhibin Benoist, Christophe Mathis, Diane Manley, Nancy R. Rudensky, Alexander Y. |
author_sort | Liston, Adrian |
collection | PubMed |
description | Foxp3 is essential for the commitment of differentiating thymocytes to the regulatory CD4(+) T (T reg) cell lineage. In humans and mice with a genetic Foxp3 deficiency, absence of this critical T reg cell population was suggested to be responsible for the severe autoimmune lesions. Recently, it has been proposed that in addition to T reg cells, Foxp3 is also expressed in thymic epithelial cells where it is involved in regulation of early thymocyte differentiation and is required to prevent autoimmunity. Here, we used genetic tools to demonstrate that the thymic epithelium does not express Foxp3. Furthermore, we formally showed that genetic abatement of Foxp3 in the hematopoietic compartment, i.e. in T cells, is both necessary and sufficient to induce the autoimmune lesions associated with Foxp3 loss. In contrast, deletion of a conditional Foxp3 allele in thymic epithelial cells did not result in detectable changes in thymocyte differentiation or pathology. Therefore, in mice the only known role for Foxp3 remains promotion of T reg cell differentiation within the T cell lineage, whereas there is no role for Foxp3 in thymic epithelial cells. |
format | Text |
id | pubmed-2137899 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21378992007-12-13 Lack of Foxp3 function and expression in the thymic epithelium Liston, Adrian Farr, Andrew G. Chen, Zhibin Benoist, Christophe Mathis, Diane Manley, Nancy R. Rudensky, Alexander Y. J Exp Med Brief Definitive Reports Foxp3 is essential for the commitment of differentiating thymocytes to the regulatory CD4(+) T (T reg) cell lineage. In humans and mice with a genetic Foxp3 deficiency, absence of this critical T reg cell population was suggested to be responsible for the severe autoimmune lesions. Recently, it has been proposed that in addition to T reg cells, Foxp3 is also expressed in thymic epithelial cells where it is involved in regulation of early thymocyte differentiation and is required to prevent autoimmunity. Here, we used genetic tools to demonstrate that the thymic epithelium does not express Foxp3. Furthermore, we formally showed that genetic abatement of Foxp3 in the hematopoietic compartment, i.e. in T cells, is both necessary and sufficient to induce the autoimmune lesions associated with Foxp3 loss. In contrast, deletion of a conditional Foxp3 allele in thymic epithelial cells did not result in detectable changes in thymocyte differentiation or pathology. Therefore, in mice the only known role for Foxp3 remains promotion of T reg cell differentiation within the T cell lineage, whereas there is no role for Foxp3 in thymic epithelial cells. The Rockefeller University Press 2007-03-19 /pmc/articles/PMC2137899/ /pubmed/17353370 http://dx.doi.org/10.1084/jem.20062465 Text en Copyright © 2007, 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 | Brief Definitive Reports Liston, Adrian Farr, Andrew G. Chen, Zhibin Benoist, Christophe Mathis, Diane Manley, Nancy R. Rudensky, Alexander Y. Lack of Foxp3 function and expression in the thymic epithelium |
title | Lack of Foxp3 function and expression in the thymic epithelium |
title_full | Lack of Foxp3 function and expression in the thymic epithelium |
title_fullStr | Lack of Foxp3 function and expression in the thymic epithelium |
title_full_unstemmed | Lack of Foxp3 function and expression in the thymic epithelium |
title_short | Lack of Foxp3 function and expression in the thymic epithelium |
title_sort | lack of foxp3 function and expression in the thymic epithelium |
topic | Brief Definitive Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2137899/ https://www.ncbi.nlm.nih.gov/pubmed/17353370 http://dx.doi.org/10.1084/jem.20062465 |
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