Evidence map›Paper›PMID 28759565›Full record

ArticlePloS one2017

Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion.

Cinthia Silva-Vilches, Katrien Pletinckx, Miriam Lohnert, Vladimir Pavlovic, Diyaaeldin Ashour, Vini John, Emilia Vendelova, Susanne Kneitz, Jie Zhou, Rena Chen and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

8 citing papers in PubMed, 15 citations in OpenAlex.

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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

14 authors at 3 institutions in 2 countries.

Cinthia Silva-VilchesInstitute of Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.
Katrien PletinckxInstitute of Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.
Miriam LohnertInstitute of Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.
Vladimir PavlovicInstitute of Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.
Diyaaeldin AshourInstitute of Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.
Vini JohnInstitute of Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.
Emilia VendelovaInstitute of Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.
Susanne KneitzInstitute of Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.
Jie ZhouBioLegend Inc., San Diego, California, United States of America.
Rena ChenBioLegend Inc., San Diego, California, United States of America.
Thomas ReinheckelInstitute of Molecular Medicine and Cell Research, and BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany.
Thomas D MuellerDepartment of Molecular Plant Physiology and Biophysics, University of Wuerzburg, Wuerzburg, Germany.
Jochen BodemInstitute of Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.
Manfred B LutzInstitute of Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.ORCID http://orcid.org/0000-0001-9193-1772
University of Würzburg · DEBioLegend (United States) · USUniversity of Freiburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3+ induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CThi, CTlo) or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β). Only DCs matured under CThi conditions secreted IL-1β, IL-6 and IL-23 leading to the instruction of Th17 cell polarization. In contrast, CTlo- or cAMP-DCs resembled semi-mature DCs and enhanced TGF-β-dependent Foxp3+ iTreg conversion. iTreg conversion could be reduced using siRNA blocking of CTLA-2 and reversely, addition of recombinant CTLA-2α increased iTreg conversion in vitro. Injection of CTlo- or cAMP-DCs exerted MOG peptide-specific protective effects in experimental autoimmune encephalomyelitis (EAE) by inducing Foxp3+ Tregs and reducing Th17 responses. Together, we identified CTLA-2 production by DCs as a novel tolerogenic mediator of TGF-β-mediated iTreg induction in vitro and in vivo. The CT-induced and cAMP-mediated up-regulation of CTLA-2 also may point to a novel immune evasion mechanism of Vibrio cholerae.

Indexed as

AnimalsAntigens, DifferentiationCathepsin LCholera ToxinCyclic AMPDendritic CellsEncephalomyelitis, Autoimmune, ExperimentalFemaleForkhead Transcription FactorsImmune SystemMaleMiceMice, Inbred C57BLPhenotypeRNA, Small InterferingTh17 CellsAntigens, DifferentiationCathepsin LCholera ToxinCyclic AMPcytotoxic T-lymphocyte antigen-2, mouseForkhead Transcription FactorsFoxp3 protein, mouseRNA, Small Interfering

Identifiers

PMID28759565
PMCPMC5536293
OpenAlexW2742095864

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.