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ID 117482
Title Alternative
A NEW LOOK AT TRANSCRIPTIONAL REGULATION BY AIRE IN mTECs
Author
Nishijima, Hitoshi Tokushima University|Tokyo Medical University KAKEN Search Researchers
Hosomichi, Kazuyoshi Kanazawa University
Akiyama, Nobuko RIKEN
Akiyama, Taishin RIKEN
Yoshida, Hideyuki RIKEN
Content Type
Journal Article
Description
The deficiency of Aire, a transcriptional regulator whose defect results in the development of autoimmunity, is associated with reduced expression of tissue-restricted self-Ags (TRAs) in medullary thymic epithelial cells (mTECs). Although the mechanisms underlying Aire-dependent expression of TRAs need to be explored, the physical identification of the target(s) of Aire has been hampered by the low and promiscuous expression of TRAs. We have tackled this issue by engineering mice with augmented Aire expression. Integration of the transcriptomic data from Aire-augmented and Aire-deficient mTECs revealed that a large proportion of so-called Aire-dependent genes, including those of TRAs, may not be direct transcriptional targets downstream of Aire. Rather, Aire induces TRA expression indirectly through controlling the heterogeneity of mTECs, as revealed by single-cell analyses. In contrast, Ccl25 emerged as a canonical target of Aire, and we verified this both in vitro and in vivo. Our approach has illuminated the Aire’s primary targets while distinguishing them from the secondary targets.
Journal Title
The Journal of Immunology
ISSN
15506606
00221767
NCID
AA12067070
AA00699656
Publisher
The American Association of Immunologists
Volume
208
Issue
2
Start Page
303
End Page
320
Published Date
2022-01-11
Rights
This article is distributed under The American Association of Immunologists, Inc.,
Reuse Terms and Conditions for Author Choice articles (https://www.jimmunol.org/info/authorchoice).
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences
Medical Sciences
University Hospital