A novel method to identify Post-Aire stages of medullary thymic epithelial cell differentiation

• Ferreirinha, Pedro

• Ribeiro, Camila

• Morimoto, Junko

• Landry, Jonathan J. M.

• Matsumoto, Minoru

• Meireles, Catarina

• White, Andrea J.

• Ohigashi, Izumi

• Araújo, Leonor

• Benes, Vladimir

• Takahama, Yousuke

• Anderson, Graham

• Matsumoto, Mitsuru

• Alves, Nuno L.

書誌事項

タイトル別名

• Leukocyte and lymphoid organ ontogeny

抄録

Autoimmune regulator+ (Aire) medullary thymic epithelial cells (mTECs) play a critical role in tolerance induction. Several studies demonstrated that Aire+mTECs differentiate further into Post-Aire cells. Yet, the identification of terminal stages of mTEC maturation depends on unique fate-mapping mouse models. Herein, we resolve this limitation by segmenting the mTEChi(MHCIIhiCD80hi) compartment into mTECA/hi (CD24−Sca1−), mTECB/hi (CD24+Sca1−), and mTECC/hi (CD24+Sca1+). While mTECA/hi included mostly Aire-expressing cells, mTECB/hi contained Aire+ and Aire− cells and mTECC/hi were mainly composed of cells lacking Aire. The differential expression pattern of Aire led us to investigate the precursor-product relationship between these subsets. Strikingly, transcriptomic analysis of mTECA/hi, mTECB/hi, and mTECC/hi sequentially mirrored the specific genetic program of Early-, Late- and Post-Aire mTECs. Corroborating their Post-Aire nature, mTECC/hi downregulated the expression of tissue-restricted antigens, acquired traits of differentiated keratinocytes, and were absent in Aire-deficient mice. Collectively, our findings reveal a new and simple blueprint to survey late stages of mTEC differentiation.

収録刊行物

• European Journal of Immunology

  European Journal of Immunology 51 (2), 311-318, 2020-08-26

  Wiley|European Federation of Immunological Societies

キーワード

• autoimmune regulator
• differentiation
• medullary thymic epithelial cell
• thymus
• tolerance induction

詳細情報

• CRID: 1050289631600934144
• NII論文ID: 120007153322
• ISSN: 15214141
• ISSN: 00142980
• DOI: 10.1002/eji.202048764
• Web Site: http://repo.lib.tokushima-u.ac.jp/116300
• Web Site: https://onlinelibrary.wiley.com/doi/pdf/10.1002/eji.202048764
• Web Site: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/eji.202048764
• 本文言語コード: en
• 資料種別: journal article
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