Modulation of Aire regulates the expression of tissue-restricted antigens

Intrathymic expression of tissue-restricted antigens (TRAs) has been viewed as the key element in the induction of central tolerance and recently, a central role for the autoimmune regulator (Aire) has been suggested in this process. The aim of this study was to establish whether down or up-regulati...

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Main Authors:	Kont, Vivian, Laan, Martti, Kisand, Kai, Merits, Andres, Scott, Hamish S., Peterson, Pärt
Format:	Online
Language:	English
Published:	Pergamon Press 2008
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994210/

id	pubmed-1994210
recordtype	oai_dc
spelling	pubmed-19942102007-10-01 Modulation of Aire regulates the expression of tissue-restricted antigens Kont, Vivian Laan, Martti Kisand, Kai Merits, Andres Scott, Hamish S. Peterson, Pärt Article Intrathymic expression of tissue-restricted antigens (TRAs) has been viewed as the key element in the induction of central tolerance and recently, a central role for the autoimmune regulator (Aire) has been suggested in this process. The aim of this study was to establish whether down or up-regulation of Aire leads to alterations in TRA expression and whether this is limited to thymic epithelial cells. This study also characterized whether TRAs follow Aire expression during normal development, and whether thymic microenvironment plays a role in the expression of Aire and TRAs. We did several in vivo and in vitro experiments to manipulate Aire expression and measured expression of four TRAs (Trefoil factor-3, Insulin-2, Major urinary protein-1 and Salivary protein-1) by real-time RT-PCR. Aire had an allele dose-dependent effect on TRA expression in the thymuses of mice from two strains, C57BL/6J and Balb/c, but had no effect on TRA expression in the lymph nodes. In the thymus, Aire and TRAs were both localized in the medulla and were co-expressed during normal development and involution. In the primary stromal cells as well as thymic epithelial cell line, the adenoviral over-expression of Aire resulted in an increase in TRA expression. By manipulating in vitro organ-cultures we showed that thymic microenvironment plays a dominant role in Aire expression whereas TRAs follow the same pattern. The data underline a direct role for Aire in TRA expression and suggest that modulation of Aire has a potential to control central tolerance and autoimmunity. Pergamon Press 2008-01 /pmc/articles/PMC1994210/ /pubmed/17599412 http://dx.doi.org/10.1016/j.molimm.2007.05.014 Text en . https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kont, Vivian Laan, Martti Kisand, Kai Merits, Andres Scott, Hamish S. Peterson, Pärt
spellingShingle	Kont, Vivian Laan, Martti Kisand, Kai Merits, Andres Scott, Hamish S. Peterson, Pärt Modulation of Aire regulates the expression of tissue-restricted antigens
author_facet	Kont, Vivian Laan, Martti Kisand, Kai Merits, Andres Scott, Hamish S. Peterson, Pärt
author_sort	Kont, Vivian
title	Modulation of Aire regulates the expression of tissue-restricted antigens
title_short	Modulation of Aire regulates the expression of tissue-restricted antigens
title_full	Modulation of Aire regulates the expression of tissue-restricted antigens
title_fullStr	Modulation of Aire regulates the expression of tissue-restricted antigens
title_full_unstemmed	Modulation of Aire regulates the expression of tissue-restricted antigens
title_sort	modulation of aire regulates the expression of tissue-restricted antigens
description	Intrathymic expression of tissue-restricted antigens (TRAs) has been viewed as the key element in the induction of central tolerance and recently, a central role for the autoimmune regulator (Aire) has been suggested in this process. The aim of this study was to establish whether down or up-regulation of Aire leads to alterations in TRA expression and whether this is limited to thymic epithelial cells. This study also characterized whether TRAs follow Aire expression during normal development, and whether thymic microenvironment plays a role in the expression of Aire and TRAs. We did several in vivo and in vitro experiments to manipulate Aire expression and measured expression of four TRAs (Trefoil factor-3, Insulin-2, Major urinary protein-1 and Salivary protein-1) by real-time RT-PCR. Aire had an allele dose-dependent effect on TRA expression in the thymuses of mice from two strains, C57BL/6J and Balb/c, but had no effect on TRA expression in the lymph nodes. In the thymus, Aire and TRAs were both localized in the medulla and were co-expressed during normal development and involution. In the primary stromal cells as well as thymic epithelial cell line, the adenoviral over-expression of Aire resulted in an increase in TRA expression. By manipulating in vitro organ-cultures we showed that thymic microenvironment plays a dominant role in Aire expression whereas TRAs follow the same pattern. The data underline a direct role for Aire in TRA expression and suggest that modulation of Aire has a potential to control central tolerance and autoimmunity.
publisher	Pergamon Press
publishDate	2008
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994210/
_version_	1611401492297678848

Modulation of Aire regulates the expression of tissue-restricted antigens

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