ID | 114327 |
Title Alternative | Notch controls the number of intraepithelial TCRαβ+CD8αα+ T cells
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Author |
Ishifune, Chieko
Tokushima University
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Tsukumo, Shin-ichi
Tokushima University
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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
Yasutomo, Koji
Tokushima University
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Content Type |
Journal Article
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Description | 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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Journal Title |
PLOS Biology
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ISSN | 15449173
15457885
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Publisher | PLOS
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Volume | 17
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Issue | 5
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Start Page | e3000262
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Published Date | 2019-05-09
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Rights | © 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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language |
eng
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departments |
Medical Sciences
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