ID | 117194 |
Author |
Morimoto, Junko
Tokushima University
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Miyazawa, Ryuichiro
Tokushima University
Yoshida, Hideyuki
RIKEN
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Content Type |
Journal Article
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Description | Impaired production of thymic regulatory T cells (Tregs) is implicated in the development of Aire-dependent autoimmunity. Because Tregs require agonistic T cell receptor stimuli by self-antigens to develop, reduced expression of self-antigens from medullary thymic epithelial cells (mTECs) has been considered to play a major role in the reduced Treg production in Aire deficiency. Here, we show that mTECs abnormally express co-inhibitory receptor CTLA-4 if Aire is non-functional. Upon binding with CD80/CD86 ligands expressed on thymic dendritic cells (DCs), the ectopically expressed CTLA-4 from Aire-deficient mTECs removes the CD80/CD86 ligands from the DCs. This attenuates the ability of DCs to provide co-stimulatory signals and to present self-antigens transferred from mTECs, both of which are required for Treg production. Accordingly, impaired production of Tregs and organ-specific autoimmunity in Aire-deficient mice are rescued by the depletion of CTLA-4 expression from mTECs. Our studies illuminate the significance of mTEC-DC interaction coordinated by Aire for the establishment of thymic tolerance.
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Journal Title |
Cell Reports
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ISSN | 22111247
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Publisher | Elsevier
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Volume | 38
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Issue | 7
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Start Page | 110384
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Published Date | 2022-02-15
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Rights | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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DOI (Published Version) | |
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language |
eng
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TextVersion |
Publisher
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departments |
Institute of Advanced Medical Sciences
Medical Sciences
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