Evidence map›Paper›PMID 31071093›Full record

ArticlePLoS biology2019

Regulation of membrane phospholipid asymmetry by Notch-mediated flippase expression controls the number of intraepithelial TCRαβ+CD8αα+ T cells.

Chieko Ishifune, Shin-Ichi Tsukumo, Yoichi Maekawa, Katsuto Hozumi, Doo Hyun Chung, Chihiro Motozono, Sho Yamasaki, Hiroyasu Nakano, Koji Yasutomo

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.1field-weighted citation impact, top 55% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. RNA Flow Cytometry for the Study of T Cell Metabolism.International journal of molecular sciences · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 6 institutions in 2 countries.

Chieko IshifuneDepartment of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
Shin-Ichi TsukumoDepartment of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
Yoichi MaekawaDepartment of Parasitology and Infectious Diseases, Gifu University Graduate School of Medicine, Gifu, Japan.ORCID 0000-0002-3879-5713
Katsuto HozumiDepartment of Immunology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Doo Hyun ChungDepartment of Pathology, Seoul National University College of Medicine, Seoul, Korea.
Chihiro MotozonoDepartment of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Sho YamasakiDepartment of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Hiroyasu NakanoDepartment of Biochemistry, School of Medicine, Toho University, Tokyo, Japan.ORCID 0000-0003-4843-1427
Koji YasutomoDepartment of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.ORCID 0000-0003-0411-2037
Tokushima University · JPThe University of Osaka · JPGifu University · JPSeoul National University · KRToho University · JPTokai University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Adenosine TriphosphatasesAnimalsCD8-Positive T-LymphocytesImmunoglobulin J Recombination Signal Sequence-Binding ProteinIntraepithelial LymphocytesMacrophagesMaleMice, Inbred C57BLPhospholipidsPhospholipid Transfer ProteinsReceptors, Antigen, T-Cell, alpha-betaReceptors, NotchAdenosine TriphosphatasesATP8a2 protein, mouseImmunoglobulin J Recombination Signal Sequence-Binding ProteinPhospholipidsPhospholipid Transfer ProteinsRbpj protein, mouseReceptors, Antigen, T-Cell, alpha-betaReceptors, Notch

Identifiers

PMID31071093
PMCPMC6529014
OpenAlexW2944207764

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.