Evidence map›Paper›PMID 33542104›Full record

ArticleAnnals of the rheumatic diseases2021

Targeting human plasmacytoid dendritic cells through BDCA2 prevents skin inflammation and fibrosis in a novel xenotransplant mouse model of scleroderma.

Rebecca L Ross, Clarissa Corinaldesi, Gemma Migneco, Ian M Carr, Agne Antanaviciute, Christopher W Wasson, Antonio Carriero, Jörg H W Distler, Steve Holmes, Yasser M El-Sherbiny and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Annals of the rheumatic diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
5.3field-weighted citation impact, top 4% 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

38 citing papers in PubMed, 53 citations in OpenAlex.

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  10. The Immune Microenvironment: New Therapeutic Implications in Organ Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 3 countries.

Rebecca L RossLeeds Institute of Rheumatic and Musculoskeletal Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK r.l.ross@leeds.ac.uk f.delgaldo@leeds.ac.uk.ORCID 0000-0002-8528-2283
Clarissa CorinaldesiLeeds Institute of Rheumatic and Musculoskeletal Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK.
Gemma MignecoLeeds Institute of Rheumatic and Musculoskeletal Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK.
Ian M CarrLeeds Institute of Medical Research, Faculty of Medicine and Health, University of Leeds, Leeds, UK.
Agne AntanaviciuteLeeds Institute of Medical Research, Faculty of Medicine and Health, University of Leeds, Leeds, UK.
Christopher W WassonLeeds Institute of Rheumatic and Musculoskeletal Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK.
Antonio CarrieroLeeds Institute of Rheumatic and Musculoskeletal Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK.ORCID 0000-0002-3112-6488
Jörg H W DistlerDepartment of Internal Medicine III, University of Erlangen, Erlangen, Germany.ORCID 0000-0001-7408-9333
Steve HolmesCapella Biosciences Ltd, Cambridge, UK.
Yasser M El-SherbinyDepartment of Biosciences, Nottingham Trent University, Nottingham, Nottinghamshire, UK.ORCID 0000-0003-4791-3475
Clive S McKimmieLeeds Institute of Medical Research, Faculty of Medicine and Health, University of Leeds, Leeds, UK.
Francesco Del GaldoLeeds Institute of Rheumatic and Musculoskeletal Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK r.l.ross@leeds.ac.uk f.delgaldo@leeds.ac.uk.ORCID 0000-0002-8528-2283
University of Leeds · GBFriedrich-Alexander-Universität Erlangen-Nürnberg · DEMansoura University · EG

Funding

Medical Research Council MC_PC_13066
6 · The paper itself

Abstract

objectivesPlasmacytoid dendritic cells (pDC) have been implicated in the pathogenesis of autoimmune diseases, such as scleroderma (SSc). However, this has been derived from indirect evidence using

methodsRNAseq of human pDC with TLR9 agonist ODN2216 and humanised monoclonal BDCA2 antibody, CBS004. Organotypic skin rafts consisting of fibroblasts and keratinocytes were stimulated with supernatant from TLR9-stimulated pDC and with CBS004. Human pDC were xenotransplanted into Nonobese diabetic/severe combined immunodeficiency (NOD SCID) mice treated with Aldara (inflammatory model), or bleomycin (fibrotic model) with CBS004 or human IgG control. Skin punch biopsies were used to assess gene and protein expression.

resultsRNAseq shows TLR9-induced activation of human pDC goes beyond type I interferon (IFN) secretion, which is functionally inactivated by BDCA2-targeting. Consistent with these findings, we show that BDCA2-targeting of pDC can completely suppress

conclusionsOur data indicate that human pDC play a key role in inflammation and immune-driven skin fibrosis, which can be effectively blocked by BDCA2-targeting, providing direct evidence supporting the development of attenuation of pDC function as a therapeutic application for SSc.

Indexed as

AnimalsDendritic CellsDisease Models, AnimalFibrosisHeterograftsHumansInflammationLectins, C-TypeMembrane GlycoproteinsMiceMice, Inbred NODMice, SCIDReceptors, ImmunologicScleroderma, LocalizedSkinCLEC4C protein, humanLectins, C-TypeMembrane GlycoproteinsReceptors, Immunologicautoimmune diseasesinflammationsclerodermasystemic

Identifiers

PMID33542104
PMCPMC8237203
OpenAlexW3127539115

What OpenQuestion holds

Textmetadata
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.