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Spontaneous autoimmunity prevented by thymic expression of a single self-antigen

The expression of self-antigen in the thymus is believed to be responsible for the deletion of autoreactive T lymphocytes, a critical process in the maintenance of unresponsiveness to self. The Autoimmune regulator (Aire) gene, which is defective in the disorder autoimmune polyglandular syndrome typ...

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Autores principales: DeVoss, Jason, Hou, Yafei, Johannes, Kellsey, Lu, Wen, Liou, Gregory I., Rinn, John, Chang, Howard, Caspi, Rachel, Fong, Lawrence, Anderson, Mark S.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118158/
https://www.ncbi.nlm.nih.gov/pubmed/17116738
http://dx.doi.org/10.1084/jem.20061864
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author DeVoss, Jason
Hou, Yafei
Johannes, Kellsey
Lu, Wen
Liou, Gregory I.
Rinn, John
Chang, Howard
Caspi, Rachel
Fong, Lawrence
Anderson, Mark S.
author_facet DeVoss, Jason
Hou, Yafei
Johannes, Kellsey
Lu, Wen
Liou, Gregory I.
Rinn, John
Chang, Howard
Caspi, Rachel
Fong, Lawrence
Anderson, Mark S.
author_sort DeVoss, Jason
collection PubMed
description The expression of self-antigen in the thymus is believed to be responsible for the deletion of autoreactive T lymphocytes, a critical process in the maintenance of unresponsiveness to self. The Autoimmune regulator (Aire) gene, which is defective in the disorder autoimmune polyglandular syndrome type 1, has been shown to promote the thymic expression of self-antigens. A clear link, however, between specific thymic self-antigens and a single autoimmune phenotype in this model has been lacking. We show that autoimmune eye disease in aire-deficient mice develops as a result of loss of thymic expression of a single eye antigen, interphotoreceptor retinoid-binding protein (IRBP). In addition, lack of IRBP expression solely in the thymus, even in the presence of aire expression, is sufficient to trigger spontaneous eye-specific autoimmunity. These results suggest that failure of thymic expression of selective single self-antigens can be sufficient to cause organ-specific autoimmune disease, even in otherwise self-tolerant individuals.
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spelling pubmed-21181582007-12-13 Spontaneous autoimmunity prevented by thymic expression of a single self-antigen DeVoss, Jason Hou, Yafei Johannes, Kellsey Lu, Wen Liou, Gregory I. Rinn, John Chang, Howard Caspi, Rachel Fong, Lawrence Anderson, Mark S. J Exp Med Articles The expression of self-antigen in the thymus is believed to be responsible for the deletion of autoreactive T lymphocytes, a critical process in the maintenance of unresponsiveness to self. The Autoimmune regulator (Aire) gene, which is defective in the disorder autoimmune polyglandular syndrome type 1, has been shown to promote the thymic expression of self-antigens. A clear link, however, between specific thymic self-antigens and a single autoimmune phenotype in this model has been lacking. We show that autoimmune eye disease in aire-deficient mice develops as a result of loss of thymic expression of a single eye antigen, interphotoreceptor retinoid-binding protein (IRBP). In addition, lack of IRBP expression solely in the thymus, even in the presence of aire expression, is sufficient to trigger spontaneous eye-specific autoimmunity. These results suggest that failure of thymic expression of selective single self-antigens can be sufficient to cause organ-specific autoimmune disease, even in otherwise self-tolerant individuals. The Rockefeller University Press 2006-11-27 /pmc/articles/PMC2118158/ /pubmed/17116738 http://dx.doi.org/10.1084/jem.20061864 Text en Copyright © 2006, 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 Articles
DeVoss, Jason
Hou, Yafei
Johannes, Kellsey
Lu, Wen
Liou, Gregory I.
Rinn, John
Chang, Howard
Caspi, Rachel
Fong, Lawrence
Anderson, Mark S.
Spontaneous autoimmunity prevented by thymic expression of a single self-antigen
title Spontaneous autoimmunity prevented by thymic expression of a single self-antigen
title_full Spontaneous autoimmunity prevented by thymic expression of a single self-antigen
title_fullStr Spontaneous autoimmunity prevented by thymic expression of a single self-antigen
title_full_unstemmed Spontaneous autoimmunity prevented by thymic expression of a single self-antigen
title_short Spontaneous autoimmunity prevented by thymic expression of a single self-antigen
title_sort spontaneous autoimmunity prevented by thymic expression of a single self-antigen
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118158/
https://www.ncbi.nlm.nih.gov/pubmed/17116738
http://dx.doi.org/10.1084/jem.20061864
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