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タイトル別表記
A NEW LOOK AT TRANSCRIPTIONAL REGULATION BY AIRE IN mTECs
著者
西嶋, 仁 Tokushima University|Tokyo Medical University KAKEN研究者をさがす
Hosomichi, Kazuyoshi Kanazawa University
Akiyama, Nobuko RIKEN
Akiyama, Taishin RIKEN
Yoshida, Hideyuki RIKEN
資料タイプ
学術雑誌論文
抄録
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.
掲載誌名
The Journal of Immunology
ISSN
15506606
00221767
cat書誌ID
AA12067070
AA00699656
出版者
The American Association of Immunologists
208
2
開始ページ
303
終了ページ
320
発行日
2022-01-11
権利情報
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
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
先端酵素学研究所
医学系
病院