Evidence map›Paper›PMID 36398893›Full record

ArticleRheumatology (Oxford, England)2023

Rheumatoid arthritis macrophages are primed for inflammation and display bioenergetic and functional alterations.

Megan M Hanlon, Trudy McGarry, Viviana Marzaioli, Success Amaechi, Qingxuan Song, Sunil Nagpal, Douglas J Veale, Ursula Fearon

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

Article in Rheumatology (Oxford, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.8field-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

36 citing papers in PubMed, 37 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 3 institutions in 2 countries.

Megan M HanlonMolecular Rheumatology Research Group, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Trudy McGarryMolecular Rheumatology Research Group, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Viviana MarzaioliMolecular Rheumatology Research Group, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.ORCID 0000-0001-9410-0835
Success AmaechiMolecular Rheumatology Research Group, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Qingxuan SongImmunology and Discovery Sciences, Janssen Research & Development, Philadelphia, PA, USA.
Sunil NagpalImmunology and Discovery Sciences, Janssen Research & Development, Philadelphia, PA, USA.
Douglas J VealeEULAR Centre of Excellence, Centre for Arthritis and Rheumatic Diseases, St Vincent's University Hospital, Dublin, Ireland.
Ursula FearonMolecular Rheumatology Research Group, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.ORCID 0000-0001-8084-0429
Trinity College Dublin · IEJanssen (United States) · USSt. Vincent's University Hospital · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesMyeloid cells with a monocyte/macrophage phenotype are present in large numbers in the RA joint, significantly contributing to disease; however, distinct macrophage functions have yet to be elucidated. This study investigates the metabolic activity of infiltrating polarized macrophages and their impact on pro-inflammatory responses in RA.

methodsCD14+ monocytes from RA and healthy control (HC) bloods were isolated and examined ex vivo or following differentiation into 'M1/M2' macrophages. Inflammatory responses and metabolic analysis ± specific inhibitors were quantified by RT-PCR, western blot, Seahorse XFe technology, phagocytosis assays and transmission electron microscopy along with RNA-sequencing (RNA-seq) transcriptomic analysis.

resultsCirculating RA monocytes are hyper-inflammatory upon stimulation, with significantly higher expression of key cytokines compared with HC (P < 0.05) a phenotype which is maintained upon differentiation into mature ex vivo polarized macrophages. This induction in pro-inflammatory mechanisms is paralleled by cellular bioenergetic changes. RA macrophages are highly metabolic, with a robust boost in both oxidative phosphorylation and glycolysis in RA along with altered mitochondrial morphology compared with HC. RNA-seq analysis revealed divergent transcriptional variance between pro- and anti-inflammatory RA macrophages, revealing a role for STAT3 and NAMPT in driving macrophage activation states. STAT3 and NAMPT inhibition results in significant decrease in pro-inflammatory gene expression observed in RA macrophages. Interestingly, NAMPT inhibition specifically restores macrophage phagocytic function and results in reciprocal STAT3 inhibition, linking these two signalling pathways.

conclusionThis study demonstrates a unique inflammatory and metabolic phenotype of RA monocyte-derived macrophages and identifies a key role for NAMPT and STAT3 signalling in regulating this phenotype.

Indexed as

Arthritis, RheumatoidMacrophagesCytokinesEnergy MetabolismHumansInflammationMonocytesCytokinesbioenergeticsmacrophagemonocyteNAMPTRASTAT3

Identifiers

PMID36398893
PMCPMC10321118
OpenAlexW4309288246

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.