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ID 114327
タイトル別表記
Notch controls the number of intraepithelial TCRαβ+CD8αα+ T cells
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
資料タイプ
学術雑誌論文
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.
掲載誌名
PLOS Biology
ISSN
15449173
15457885
出版者
PLOS
17
5
開始ページ
e3000262
発行日
2019-05-09
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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出版社版URL
フルテキストファイル
言語
eng
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出版社版
部局
医学系