Notch controls the number of intraepithelial TCRαβ+CD8αα+ T cells
Ishifune, Chieko Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Tsukumo, Shin-ichi Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
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 Tokushima University Educator and Researcher Directory KAKEN Search Researchers
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.
© 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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