Evidence mapPaperPMID 38069152Full record

ArticleInternational journal of molecular sciences2023

Sitagliptin Induces Tolerogenic Human Dendritic Cells.

Marija Drakul, Sergej Tomić, Marina Bekić, Dušan Mihajlović, Miloš Vasiljević, Sara Rakočević, Jelena Đokić, Nikola Popović, Dejan Bokonjić, Miodrag Čolić

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.4field-weighted citation impact, top 15% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. 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

10 authors at 3 institutions in 2 countries.

Marija DrakulMedical Faculty Foca, University of East Sarajevo, 73300 Foča, R. Srpska, Bosnia and Herzegovina.
Sergej TomićInstitute for the Application of Nuclear Energy, University of Belgrade, 11000 Belgrade, Serbia.ORCID 0000-0003-2570-1295
Marina BekićInstitute for the Application of Nuclear Energy, University of Belgrade, 11000 Belgrade, Serbia.ORCID 0000-0002-6945-4241
Dušan MihajlovićMedical Faculty Foca, University of East Sarajevo, 73300 Foča, R. Srpska, Bosnia and Herzegovina.ORCID 0000-0002-8922-9914
Miloš VasiljevićMedical Faculty Foca, University of East Sarajevo, 73300 Foča, R. Srpska, Bosnia and Herzegovina.
Sara RakočevićMedical Faculty Foca, University of East Sarajevo, 73300 Foča, R. Srpska, Bosnia and Herzegovina.
Jelena ĐokićInstitute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11000 Belgrade, Serbia.
Nikola PopovićInstitute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11000 Belgrade, Serbia.ORCID 0000-0002-0036-3958
Dejan BokonjićMedical Faculty Foca, University of East Sarajevo, 73300 Foča, R. Srpska, Bosnia and Herzegovina.ORCID 0000-0002-7749-5326
Miodrag ČolićMedical Faculty Foca, University of East Sarajevo, 73300 Foča, R. Srpska, Bosnia and Herzegovina.
University of East Sarajevo · BAUniversity of Belgrade · RSSerbian Academy of Sciences and Arts · RS

Funding

Serbian Academy of Sciences and Arts project F115The Ministry of Science, Technological Development and Innovation, Republic of Serbia Contract No. 451-03-47/2023-01/ 200019; Contract No. 451-03-47/2023-01/ 200042University of East Sarajevo, Medical Faculty Foča, Foča, Bosnia and Herzegovina project UIS/MFF: I.1.20-22
6 · The paper itself

Abstract

Sitagliptin, an anti-diabetic drug, is a dipeptidyl peptidase (DPP)-4/CD26 inhibitor with additional anti-inflammatory and immunomodulatory properties. In this study, we investigated for the first time the effect of sitagliptin on the differentiation and functions of human dendritic cells generated from monocytes (MoDCs) for 4 days using the standard GM-CSF/IL-4 procedure. LPS/IFN-γ treatment for an additional 24 h was used for maturation induction of MoDCs. Sitagliptin was added at the highest non-cytotoxic concentration (500 µg/mL) either at the beginning (sita 0d protocol) or after MoDC differentiation (sita 4d protocol). Sitagliptin impaired differentiation and maturation of MoDCs as judged with the lower expression of CD40, CD83, CD86, NLRP3, and HLA-DR, retention of CD14 expression, and inhibited production of IL-β, IL-12p70, IL-23, and IL-27. In contrast, the expression of CD26, tolerogenic DC markers (ILT4 and IDO1), and production of immunoregulatory cytokines (IL-10 and TGF-β) were increased. Generally, the sita 0d protocol was more efficient. Sitagliptin-treated MoDCs were poorer allostimulators of T-cells in MoDC/T-cell co-culture and inhibited Th1 and Th17 but augmented Th2 and Treg responses. Tolerogenic properties of sitagliptin-treated MoDCs were additionally confirmed by an increased frequency of CD4+CD25+CD127- FoxP3+ Tregs and Tr1 cells (CD4+IL-10+FoxP3-) in MoDC/T-cell co-culture. The differentiation of IL-10+ and TGF-β+ Tregs depended on the sitagliptin protocol used. A Western blot analysis showed that sitagliptin inhibited p65 expression of NF-kB and p38MAPK during the maturation of MoDCs. In conclusion, sitagliptin induces differentiation of tolerogenic DCs, and the effect is important when considering sitagliptin for treating autoimmune diseases and allotransplant rejection.

Indexed as

Dipeptidyl Peptidase 4Interleukin-10Cell DifferentiationCells, CulturedDendritic CellsForkhead Transcription FactorsHumansMonocytesSitagliptin PhosphateTransforming Growth Factor betaDipeptidyl Peptidase 4Forkhead Transcription FactorsInterleukin-10Sitagliptin PhosphateTransforming Growth Factor betaCD26 expressiondendritic cellsdipeptidyl peptidase 4 inhibitorsregulatory T cellstolerance

Identifiers

PMID38069152
PMCPMC10706581
OpenAlexW4389045568

What Socratic holds

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LicenceCC BY
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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 Socratic graph.