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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...

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Autores principales: Liston, Adrian, Farr, Andrew G., Chen, Zhibin, Benoist, Christophe, Mathis, Diane, Manley, Nancy R., Rudensky, Alexander Y.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
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.
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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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