| First Author | Ishifune C | Year | 2019 |
| Journal | PLoS Biol | Volume | 17 |
| Issue | 5 | Pages | e3000262 |
| PubMed ID | 31071093 | Mgi Jnum | J:275839 |
| Mgi Id | MGI:6306793 | Doi | 10.1371/journal.pbio.3000262 |
| Citation | Ishifune C, et al. (2019) Regulation of membrane phospholipid asymmetry by Notch-mediated flippase expression controls the number of intraepithelial TCRalphabeta+CD8alphaalpha+ T cells. PLoS Biol 17(5):e3000262 |
| abstractText | Intestinal intraepithelial lymphocytes (IELs) expressing CD8alphaalpha on alphabeta T cells (TCRalphabeta+CD8alphaalpha+ 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 TCRalphabeta+CD8alphaalpha+ 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 TCRalphabeta+CD8alphaalpha+ 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 TCRalphabeta+CD8alphaalpha+ IELs cannot maintain phosphatidylserine in the inner leaflet of the plasma membrane. Furthermore, depletion of intestinal macrophages restored TCRalphabeta+CD8alphaalpha+ IELs in Rbpj-deficient mice, suggesting that exposure of phosphatidylserine on the plasma membrane in Rbpj-deficient TCRalphabeta+CD8alphaalpha+ 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 TCRalphabeta+CD8alphaalpha+ IELs. |
