Evidence map›Paper›PMID 25714914›Full record

ArticlePloS one2015

Induction of indoleamine 2, 3-dioxygenase in human dendritic cells by a cholera toxin B subunit-proinsulin vaccine.

Jacques C Mbongue, Dequina A Nicholas, Kangling Zhang, Nan-Sun Kim, Brittany N Hamilton, Marco Larios, Guangyu Zhang, Kazuo Umezawa, Anthony F Firek, William H R Langridge

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.8field-weighted citation impact, top 17% 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

16 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
  2. Article
  3. Vaccine for Diabetes-Where Do We Stand?International journal of molecular sciences · 2022
    Review
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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

10 authors at 3 institutions in 3 countries.

Jacques C MbongueCenter for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, United States of America; Loma Linda University School of Medicine, Department of Basic Sciences, Division of Physiology, Loma Linda, CA, United States of America.
Dequina A NicholasCenter for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, United States of America; Mass Spectrometer Core Facility, Department of Biochemistry, Loma Linda University School of Medicine, Loma Linda University School of Medicine, Department of Basic Sciences, Loma Linda, CA, United States of America.
Kangling ZhangMass Spectrometer Core Facility, Department of Biochemistry, Loma Linda University School of Medicine, Loma Linda University School of Medicine, Department of Basic Sciences, Loma Linda, CA, United States of America; Department of Pharmacology and Toxicology, School of Medicine, University of Texas Medical Branch, Galveston, TX, United States of America.
Nan-Sun KimCenter for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, United States of America; Mass Spectrometer Core Facility, Department of Biochemistry, Loma Linda University School of Medicine, Loma Linda University School of Medicine, Department of Basic Sciences, Loma Linda, CA, United States of America; Department of Molecular Biology, Chonbuk National University, Jeon-Ju, Republic of Korea.
Brittany N HamiltonCenter for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, United States of America; Loma Linda University School of Medicine, Department of Basic Sciences, Division of Microbiology and Molecular Genetics, Loma Linda, CA, United States of America.
Marco LariosCenter for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, United States of America.
Guangyu ZhangMass Spectrometer Core Facility, Department of Biochemistry, Loma Linda University School of Medicine, Loma Linda University School of Medicine, Department of Basic Sciences, Loma Linda, CA, United States of America.
Kazuo UmezawaAichi Medical University, School of Medicine, Department of Molecular Target Medicine Screening, Nagakute, Aichi, Japan.
Anthony F FirekEndocrinology Section, JL Pettis Memorial VA Medical Center, Loma Linda, CA, United States of America.
William H R LangridgeCenter for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, United States of America; Mass Spectrometer Core Facility, Department of Biochemistry, Loma Linda University School of Medicine, Loma Linda University School of Medicine, Department of Basic Sciences, Loma Linda, CA, United States of America.
Loma Linda University · USAichi Medical University · JPJerry L. Pettis Memorial VA Medical Center · US

Funding

NIH-LLU Initiative for Maximizing Student DiversityR25GM060507 · NIGMS · LOMA LINDA UNIVERSITY · PI DE LEON, MARINO · 2001 to 2022
$11.3M
Research Training/Education CoreP20MD006988 · NIMHD · LOMA LINDA UNIVERSITY · PI DE LEON, MARINO · 2012 to 2016
$6.2M
LTQ-Orbitrap-XL-ETD Mass Spectrometer for LLU Mass Spectrometry FacilityS10RR027643 · NCRR · LOMA LINDA UNIVERSITY · PI ZHANG, KANGLING · 2010 to 2010
$500k
NCRR NIH HHS 1S10RR027643NCRR NIH HHS S10 RR027643NIDDK NIH HHS DK-99-013NIGMS NIH HHS R25 GM060507NIMHD NIH HHS 5P20MD006988NIMHD NIH HHS P20 MD006988
6 · The paper itself

Abstract

Dendritic cells (DC) interact with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this study, immature human dendritic cells (iDC) were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS). Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1). Increased biosynthesis of the immunosuppressive enzyme was detected in DCs inoculated with the CTB-INS fusion protein but not in DCs inoculated with proinsulin, CTB, or an unlinked combination of the two proteins. Immunoblot and PCR analyses of vaccine treated DCs detected IDO1mRNA by 3 hours and IDO1 protein synthesis by 6 hours after vaccine inoculation. Determination of IDO1 activity in vaccinated DCs by measurement of tryptophan degradation products (kynurenines) showed increased tryptophan cleavage into N-formyl kynurenine. Vaccination did not interfere with monocytes differentiation into DC, suggesting the vaccine can function safely in the human immune system. Treatment of vaccinated DCs with pharmacological NF-κB inhibitors ACHP or DHMEQ significantly inhibited IDO1 biosynthesis, suggesting a role for NF-κB signaling in vaccine up-regulation of dendritic cell IDO1. Heat map analysis of the proteomic data revealed an overall down-regulation of vaccinated DC functions, suggesting vaccine suppression of DC maturation. Together, our experimental data indicate that CTB-INS vaccine induction of IDO1 biosynthesis in human DCs may result in the inhibition of DC maturation generating a durable state of immunological tolerance. Understanding how CTB-INS modulates IDO1 activity in human DCs will facilitate vaccine efficacy and safety, moving this immunosuppressive strategy closer to clinical applications for prevention of type 1 diabetes autoimmunity.

Indexed as

Cell DifferentiationCholera ToxinCluster AnalysisDendritic CellsGene Expression ProfilingHumansIndoleamine-Pyrrole 2,3,-DioxygenaseMonocytesNF-kappa BProinsulinProteomeProteomicsSignal TransductionVaccines, SubunitCholera ToxinIndoleamine-Pyrrole 2,3,-DioxygenaseNF-kappa BProinsulinProteomeVaccines, Subunit

Identifiers

PMID25714914
PMCPMC4340906
OpenAlexW1963756724

What OpenQuestion holds

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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.