ID 112343
Title Alternative
Identification of mTEC precursor cells
Author
Akiyama, Nobuko The University of Tokyo
Takizawa, Nobukazu The University of Tokyo
Miyauchi, Maki The University of Tokyo
Yanai, Hiromi The University of Tokyo
Tateishi, Ryosuke The University of Tokyo
Shinzawa, Miho The University of Tokyo
Yoshinaga, Riko The University of Tokyo
Kurihara, Masaaki National Institute of Health Sciences
Demizu, Yosuke National Institute of Health Sciences
Yasuda, Hisataka Oriental Yeast Co., Ltd.
Yagi, Shintaro The University of Tokyo
Wu, Guoying The University of Tokyo
Sakamoto, Reiko The University of Tokyo
Yoshida, Nobuaki The University of Tokyo
Penninger, Josef M. Institute of Molecular Biotechnology of the Austrian Academy of Sciences
Kobayashi, Yasuhiro Matsumoto Dental University
Inoue, Jun-ichiro The University of Tokyo
Akiyama, Taishin The University of Tokyo
Content Type
Journal Article
Description
Medullary thymic epithelial cells (mTECs) expressing autoimmune regulator (Aire) are critical for preventing the onset of autoimmunity. However, the differentiation program of Aire-expressing mTECs (Aire+ mTECs) is unclear. Here, we describe novel embryonic precursors of Aire+ mTECs. We found the candidate precursors of Aire+ mTECs (pMECs) by monitoring the expression of receptor activator of nuclear factor-κB (RANK), which is required for Aire+ mTEC differentiation. pMECs unexpectedly expressed cortical TEC molecules in addition to the mTEC markers UEA-1 ligand and RANK and differentiated into mTECs in reaggregation thymic organ culture. Introduction of pMECs in the embryonic thymus permitted long-term maintenance of Aire+ mTECs and efficiently suppressed the onset of autoimmunity induced by Aire+ mTEC deficiency. Mechanistically, pMECs differentiated into Aire+ mTECs by tumor necrosis factor receptor-associated factor 6-dependent RANK signaling. Moreover, nonclassical nuclear factor-κB activation triggered by RANK and lymphotoxin-β receptor signaling promoted pMEC induction from progenitors exhibiting lower RANK expression and higher CD24 expression. Thus, our findings identified two novel stages in the differentiation program of Aire+ mTECs.
Journal Title
Journal of Experimental Medicine
ISSN
15409538
00221007
NCID
AA12119243
AA00697559
Publisher
Rockefeller University Press
Volume
213
Issue
8
Start Page
1441
End Page
1458
Published Date
2016-07-11
Rights
© 2016 Akiyama et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
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DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences