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ID 117817
Title Alternative
Dysregulated Aire expression and autoimmunity
Author
Sugita, Mizuki Tokushima University
Umezawa, Natsuka Tokyo Medical and Dental University
Kimura, Naoki Tokyo Medical and Dental University
Sasaki, Hirokazu
Keywords
Aire
autoimmune disease
EAE
mTEC
polymyositis
self-tolerance
Content Type
Journal Article
Description
Deficiency for AIRE/Aire in both humans and mice results in the development of organ-specific autoimmune disease. We tested whether augmented and/or dysregulated AIRE/Aire expression might be also prone to the breakdown of self-tolerance. To define the effect of augmented Aire expression on the development of autoimmunity, antigen-specific clonal deletion and production of clonotypic regulatory T cells (Tregs) in the thymus were examined using mice expressing two additional copies of Aire in a heterozygous state (3xAire-knockin mice: 3xAire-KI). We found that both clonal deletion of autoreactive T cells and production of clonotypic Tregs in the thymus from 3xAire-KI were impaired in a T-cell receptor-transgenic system. Furthermore, 3xAire-KI females showed higher scores of experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein than wild-type littermates, suggesting that augmented Aire expression exacerbates organ-specific autoimmunity under disease-prone conditions. In humans, we found that one patient with amyopathic dermatomyositis showed CD3–CD19– cells expressing AIRE in the peripheral blood before the treatment but not during the remission phase treated with immunosuppressive drugs. Thus, not only loss of function of AIRE/Aire but also augmented and/or dysregulated expression of AIRE/Aire should be considered for the pathogenesis of organ-specific autoimmunity. We suggest that further analyses should be pursued to establish a novel link between organ-specific autoimmune disease and dysregulated AIRE expression in clinical settings.
Journal Title
Immunology & Cell Biology
ISSN
14401711
NCID
AA10678685
Publisher
Australian and New Zealand Society for Immunology|Wiley
Volume
100
Issue
5
Start Page
371
End Page
377
Published Date
2022-03-21
Rights
This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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DOI (Published Version)
URL ( Publisher's Version )
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language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences
University Hospital
Medical Sciences