number of access : ?
number of downloads : ?
ID 114944
Title Alternative
胸腺および末梢トレランスにおいてAireにより制御される臓器特異的自己免疫応答
Amelioration of diabetes in NOD by additive Aire
Author
Hosomichi, Kazuyoshi Kanazawa University
Keywords
Aire
1型糖尿病
Xcr1陽性樹状細胞
NOD
mTEC
type 1 diabetes
Xcr1+ DC
Content Type
Thesis or Dissertation
Description
Tissue-specific autoimmune diseases are assumed to arise through malfunction of two checkpoints for immune tolerance: defective elimination of autoreactive T cells in the thymus and activation of these T cells by corresponding autoantigens in the periphery. However, evidence for this model and the outcome of such alterations in each or both of the tolerance mechanisms have not been sufficiently investigated. We studied these issues by expressing human AIRE (huAIRE) as a modifier of tolerance function in NOD mice wherein the defects of thymic and peripheral tolerance together cause type I diabetes (T1D). Additive huAIRE expression in the thymic stroma had no major impact on the production of diabetogenic T cells in the thymus. In contrast, huAIRE expression in peripheral antigen-presenting cells (APCs) rendered the mice resistant to T1D, while maintaining other tissue-specific autoimmune responses and antibody production against an exogenous protein antigen, because of the loss of Xcr1+ dendritic cells, an essential component for activating diabetogenic T cells in the periphery. These results contrast with our recent demonstration that huAIRE expression in both the thymic stroma and peripheral APCs resulted in the paradoxical development of muscle-specific autoimmunity. Our results reveal that tissue-specific autoimmunity is differentially controlled by a combination of thymic function and peripheral tolerance, which can be manipulated by expression of huAIRE/Aire in each or both of the tolerance mechanisms.
Journal Title
International Immunology
ISSN
14602377
NCID
AA12096432
Publisher
Oxford University Press|The Japanese Society for Immunology
Volume
32
Issue
2
Start Page
117
End Page
131
Published Date
2019-10-05
Remark
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Minoru Matsumotoの学位論文として提出され, 学位審査・授与の対象となっている。
Rights
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/ ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3429号
Diploma Number
甲医第1459号
Granted Date
2020-06-25
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences
Institute of Advanced Medical Sciences