Evidence map›Paper›PMID 27671847›Full record

ArticleStem cells (Dayton, Ohio)2017

Mesenchymal Stromal Cell Secretion of Programmed Death-1 Ligands Regulates T Cell Mediated Immunosuppression.

Lindsay C Davies, Nina Heldring, Nadir Kadri, Katarina Le Blanc

Open access · bronzeAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 229 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
229citing papers in PubMed, 1 pooled it
10.9field-weighted citation impact, top 1% 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

229 citing papers in PubMed, 1 synthesis or guideline pooled it, 339 citations in OpenAlex.

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169 more citing papers are in PubMed but not listed here.

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

4 authors at 3 institutions in 2 countries.

Lindsay C DaviesCenter for Hematology and Regenerative Medicine (HERM).
Nina HeldringCenter for Hematology and Regenerative Medicine (HERM).
Nadir KadriCenter for Hematology and Regenerative Medicine (HERM).
Katarina Le BlancCenter for Hematology and Regenerative Medicine (HERM).
Institute for Transfusion Medicine · USCenter for Neuroscience and Regenerative Medicine · USKarolinska Institutet · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mesenchymal stromal cells (MSCs) exert broad immunosuppressive potential, modulating the activity of cells of innate and adaptive immune systems. As MSCs become accepted as a therapeutic option for the treatment of immunological disorders such as Graft versus Host Disease, our need to understand the intricate details by which they exert their effects is crucial. Programmed death-1 (PD-1) is an important regulator in T cell activation and homeostatic control. It has been reported that this pathway may be important in contact-dependent mediated immunomodulation by MSCs. The aim of this study was to establish whether MSCs, in addition to their cell-surface expression, are able to secrete PD-1 ligands (PD-L1 and PD-L2) and their potential importance in modulating contact-independent mechanisms of MSC immunosuppression. Here we report that MSCs express and secrete PD-L1 and PD-L2 and that this is regulated by exposure to interferon γ and tumor necrosis factor α. MSCs, via their secretion of PD-1 ligands, suppress the activation of CD4+ T cells, downregulate interleukin-2 secretion and induce irreversible hyporesponsiveness and cell death. Suppressed T cells demonstrated a reduction in AKT phosphorylation at T308 and a subsequent increase in FOXO3 expression that could be reversed with blockade of PD-L1. In conclusion, we demonstrate for the first time, that MSCs are able to secrete PD-1 ligands, with this being the first known report of a biological role for PD-L2 in MSCs. These soluble factors play an important role in modulating immunosuppressive effects of MSCs directly on T cell behavior and induction of peripheral tolerance. Stem Cells 2017;35:766-776.

Indexed as

Immunosuppression TherapyApoptosisB7-H1 AntigenDown-RegulationHumansInterleukin-2LigandsLymphocyte ActivationMesenchymal Stem CellsModels, BiologicalPhosphorylationProteomeProto-Oncogene Proteins c-aktSignal TransductionSolubilityT-LymphocytesB7-H1 AntigenCD274 protein, humanInterleukin-2LigandsProteomeProto-Oncogene Proteins c-aktAdult human bone marrowAdult stem cellsCytokinesImmunomodulationMarrow stromal stem cellsProgrammed-death 1T cells

Identifiers

PMID27671847
PMCPMC5599995
OpenAlexW2526446404

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.