NDLI: Age-related deregulation of Aire and peripheral tissue antigen genes in the thymic stroma of non-obese diabetic (NOD) mice is associated with autoimmune type 1 diabetes mellitus (DM-1)

Content Provider	Springer Nature Link
Author	Fornari, Thaís A. Donate, Paula B. Macedo, Claudia Marques, Márcia M. C. Magalhães, Danielle A. Passos, Geraldo A. S.
Copyright Year	2010
Abstract	Gene expression of peripheral tissue antigens (PTAs) in stromal medullary thymic epithelial cells (mTECs) is a key process to the negative selection of autoreactive thymocytes. This phenomenon was termed “promiscuous gene expression” (PGE), which is partially controlled by the Aire gene. Nevertheless, reasons for the correlation of Aire and PTAs with the emergence of autoimmune diseases are largely unknown, though it may be a result of a chronological effect. Although the effect of Aire mutations in pathogenic autoimmunity is well know, it could not be a unique cause for autoimmunity. Independently of mutations, temporal deregulation of Aire expression may imbalance Aire-dependent PTAs and/or wide PGE. This deregulation may be an early warning sign for autoimmune diseases as it guarantees autoantigen representation in the thymus. To assess this hypothesis, we studied the expression levels of Aire, Aire-dependent (Ins2) and Aire-independent (Gad67 and Col2a1) PTAs using real-time-PCR of the thymic stromal cells of NOD mice during the development of autoimmune type 1 diabetes mellitus (DM-1). Wide PGE was studied by microarrays in which the PTA genes were identified through parallel CD80$^{+}$ mTEC 3.10 cell line expression profiling. The results show that Aire gene was down-regulated in young pre-autoimmune (pre-diabetic) NOD mice. PGE and specific PTA genes were down-regulated in adult autoimmune diabetic animals. These findings represent evidence indicating that chronological deregulation of genes important to negative selection may be associated with the development of an autoimmune disease (DM-1) in mice.
Starting Page	21
Ending Page	28
Page Count	8
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	342
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Springer US
Publisher Date	2010-04-23
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Aire gene Chronological gene expression Non-obese diabetic (NOD) Thymic stromal cells Type 1 diabetes mellitus Cardiology Oncology Medical Biochemistry Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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