ID | 114327 |
タイトル別表記 | Notch controls the number of intraepithelial TCRαβ+CD8αα+ T cells
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著者 |
Maekawa, Yoichi
Gifu University
Hozumi, Katsuto
Tokai University
Chung, Doo Hyun
Seoul National University
Motozono, Chihiro
Osaka University
Yamasaki, Sho
Osaka University
Nakano, Hiroyasu
Toho University
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資料タイプ |
学術雑誌論文
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抄録 | Intestinal intraepithelial lymphocytes (IELs) expressing CD8αα on αβ T cells (TCRαβ+CD8αα+ IELs) have suppressive capabilities in enterocolitis, but the mechanism that maintains homeostasis and cell number is not fully understood. Here, we demonstrated that the number of TCRαβ+CD8αα+ IELs was severely reduced in mice lacking recombination signal binding protein for immunoglobulin kappa J region (Rbpj) or Notch1 and Notch2 in T cells. Rbpj-deficient TCRαβ+CD8αα+ IELs expressed low levels of Atp8a2, which encodes a protein with flippase activity that regulates phospholipid asymmetry of plasma membrane such as flipping phosphatidylserine in the inner leaflet of plasma membrane. Rbpj-deficient TCRαβ+CD8αα+ IELs cannot maintain phosphatidylserine in the inner leaflet of the plasma membrane. Furthermore, depletion of intestinal macrophages restored TCRαβ+CD8αα+ IELs in Rbpj-deficient mice, suggesting that exposure of phosphatidylserine on the plasma membrane in Rbpj-deficient TCRαβ+CD8αα+ IELs acts as an “eat-me” signal. Together, these results revealed that Notch–Atp8a2 is a fundamental regulator for IELs and highlighted that membrane phospholipid asymmetry controlled by Notch-mediated flippase expression is a critical determinant in setting or balancing the number of TCRαβ+CD8αα+ IELs.
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掲載誌名 |
PLOS Biology
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ISSN | 15449173
15457885
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出版者 | PLOS
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巻 | 17
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号 | 5
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開始ページ | e3000262
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発行日 | 2019-05-09
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権利情報 | © 2019 Ishifune et al. This is an open access article distributed under the terms of the Creative Commons Attribution License( https://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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言語 |
eng
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出版社版
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部局 |
医学系
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