Evidence map›Paper›PMID 29105068›Full record

ArticleClinical and experimental immunology2018

Activation of plasmacytoid dendritic cells by apoptotic particles - mechanism for the loss of immunological tolerance in Sjögren's syndrome.

M Ainola, P Porola, Y Takakubo, B Przybyla, V P Kouri, T A Tolvanen, A Hänninen, D C Nordström

Open access · bronzeAbstract read
In one paragraph

Article in Clinical and experimental immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

48 citing papers in PubMed, 68 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

8 authors at 4 institutions in 2 countries.

M AinolaDepartment of Medicine, Clinicum, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland.ORCID 0000-0003-2853-5851
P PorolaDepartment of Medicine, Clinicum, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland.
Y TakakuboDepartment of Orthopaedic Surgery, Yamagata University, Yamagata, Japan.
B PrzybylaHematology and Cancer Center, Helsinki University Central Hospital, Helsinki, Finland.
V P KouriDepartment of Medicine, Clinicum, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland.
T A TolvanenDepartment of Pathology, University of Helsinki, Helsinki, Finland.
A HänninenDepartment of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
D C NordströmDepartment of Internal Medicine and Rehabilitation, Helsinki University Central Hospital, and University of Helsinki, Helsinki, Finland.
University of Helsinki · FIHelsinki University Hospital · FIUniversity of Turku · FIYamagata University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sjögren's syndrome (SS) is a common autoimmune disease targeting salivary and lacrimal glands. It is strongly female-dominant, characterized by low oestrogen levels combined with a local intracrine dihydrotestosterone defect. We hypothesized that these hormonal deficits lead to increased apoptosis of the epithelial cells and plasmacytoid dendritic cell (pDC)-mediated proinflammatory host responses. Expression of Toll-like receptors (TLRs)-7 and -9 and cytokine profiles was studied in pDCs treated with apoptotic particles collected in consecutive centrifugation steps of media from apoptotic cells. Expression and localization of SS autoantigens in these particles was also analysed. Furthermore, the effects of sex steroids were studied in pDCs cultured with several concentrations of dihydrotestosterone and 17-β-oestradiol, and in saliva of patient treated with dehydroepiandrosterone. Apoptosis of the epithelial cells led to cleavage and translocation of SS-autoantigens, α-fodrin and SS-A, into apoptotic particles. The apoptosis-induced apoptotic particles also contained another SS-autoantigen, hy1-RNA. These particles were internalized by pDCs in a size-dependent manner and affected TLR-7 and -9 expression and the production of proinflammatory cytokines. The analysed androgens protected cells from apoptosis, influenced redistribution of autoantigens and diminished the apoptotic particle-stimulated increase of the TLRs in pDCs. Our findings suggest that the formation of apoptotic particles may play a role in loss of immune tolerance, manifested by production of autoantibodies and the onset of autoinflammation in SS.

Indexed as

AdultAgedApoptosisCarrier ProteinsCell DifferentiationCells, CulturedCytokinesDendritic CellsDihydrotestosteroneEpithelial CellsEstrogensExtracellular VesiclesFemaleHumansImmune ToleranceInflammation MediatorsCarrier ProteinsCytokinesDihydrotestosteroneEstrogensInflammation MediatorsMicrofilament ProteinsRibonucleoproteinsSpectrinSS-A AntigenToll-Like Receptor 7Toll-Like Receptor 9apoptosisautoimmunitycytokinesdendritic cellsToll-like receptors (TLRs)

Identifiers

PMID29105068
PMCPMC5801512
OpenAlexW2766959433

What OpenQuestion holds

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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.