Evidence map›Paper›PMID 35168946›Full record

ArticleAnnals of the rheumatic diseases2022

Ageing and interferon gamma response drive the phenotype of neutrophils in the inflamed joint.

Ricardo Grieshaber-Bouyer, Tarik Exner, Nicolaj S Hackert, Felix A Radtke, Scott A Jelinsky, Olha Halyabar, Alexandra Wactor, Elham Karimizadeh, Joseph Brennan, Jorge Schettini and 9 more

Open access · greenAbstract read
In one paragraph

Article in Annals of the rheumatic diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

25 citing papers in PubMed, 35 citations in OpenAlex.

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  13. The 'TNature reviews. Rheumatology · 2025
    Review
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  15. Review
  16. Review
  17. Review
  18. Ferroptosis in Arthritis: Driver of the Disease or Therapeutic Option?International journal of molecular sciences · 2024
    Review
  19. Article
  20. Article
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

19 authors at 4 institutions in 2 countries.

Ricardo Grieshaber-BouyerDivision of Rheumatology, Department of Medicine V (Hematology, Oncology and Rheumatology), Heidelberg University Hospital, Heidelberg, Germany Ricardo.GrieshaberBouyer@med.uni-heidelberg.de peter.nigrovic@childrens.harvard.edu.ORCID http://orcid.org/0000-0002-2873-5135
Tarik ExnerDivision of Rheumatology, Department of Medicine V (Hematology, Oncology and Rheumatology), Heidelberg University Hospital, Heidelberg, Germany.
Nicolaj S HackertDivision of Rheumatology, Department of Medicine V (Hematology, Oncology and Rheumatology), Heidelberg University Hospital, Heidelberg, Germany.
Felix A RadtkeDivision of Rheumatology, Department of Medicine V (Hematology, Oncology and Rheumatology), Heidelberg University Hospital, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-6491-2573
Scott A JelinskyComputational Systems Immunology, Worldwide Research & Development, Pfizer Inc, Cambridge, Massachusetts, USA.
Olha HalyabarDivision of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Alexandra WactorDivision of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Elham KarimizadehDivision of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Joseph BrennanComputational Systems Immunology, Worldwide Research & Development, Pfizer Inc, Cambridge, Massachusetts, USA.
Jorge SchettiniComputational Systems Immunology, Worldwide Research & Development, Pfizer Inc, Cambridge, Massachusetts, USA.
Helena JonssonDivision of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Deepak A RaoDivision of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.ORCID http://orcid.org/0000-0001-9672-7746
Lauren A HendersonDivision of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Carsten Müller-TidowMolecular Medicine Partnership Unit, European Molecular Biology Laboratory (EMBL), University of Heidelberg, Heidelberg, Germany.
Hanns-Martin LorenzDivision of Rheumatology, Department of Medicine V (Hematology, Oncology and Rheumatology), Heidelberg University Hospital, Heidelberg, Germany.
Guido WabnitzInstitute for Immunology, Heidelberg University Hospital, Heidelberg, Germany.
James A LedererDepartment of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Angela HadjipanayisComputational Systems Immunology, Worldwide Research & Development, Pfizer Inc, Cambridge, Massachusetts, USA.
Peter A NigrovicDivision of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA Ricardo.GrieshaberBouyer@med.uni-heidelberg.de peter.nigrovic@childrens.harvard.edu.ORCID http://orcid.org/0000-0002-2126-3702
Brigham and Women's Hospital · USHeidelberg University · DEPfizer (United States) · USBoston Children's Hospital · US

Funding

ImmGen: Gene Expression and Regulation in Immune CellsR24AI072073 · NIAID · JOSLIN DIABETES CENTER · PI CHRISTOPHE O. BENOIST · 2007 to 2026
$28.5M
Joint Biology Consortium Resource-based CenterP30AR070253 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Peter A Nigrovic, Jeffrey Andrew Sparks · 2016 to 2026
$9.4M
Ly6 family members in neutrophil biologyR01AR065538 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI NIGROVIC, PETER A · 2014 to 2024
$4.0M
Bridging the gap between GWAS and mechanism in JIAR01AR073201 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Peter A Nigrovic · 2019 to 2026
$3.2M
T resident memory cells in arthritisR01AR075906 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI NIGROVIC, PETER A · 2019 to 2023
$2.1M
Modulation of neutrophil function through emperipolesisR21AR076630 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI NIGROVIC, PETER A · 2020 to 2021
$545k
Impact of emperipolesis on platelet functionR21HL150575 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI NIGROVIC, PETER A · 2020 to 2021
$470k
Ly6 family members in neutrophil biologyR56AR065538 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI NIGROVIC, PETER A · 2019 to 2019
$411k
NHLBI NIH HHS R21 HL150575NIAID NIH HHS R24 AI072073NIAMS NIH HHS P30 AR070253NIAMS NIH HHS R01 AR065538NIAMS NIH HHS R01 AR073201NIAMS NIH HHS R01 AR075906NIAMS NIH HHS R21 AR076630NIAMS NIH HHS R56 AR065538
6 · The paper itself

Abstract

objectiveNeutrophils are typically the most abundant leucocyte in arthritic synovial fluid. We sought to understand changes that occur in neutrophils as they migrate from blood to joint.

methodsWe performed RNA sequencing of neutrophils from healthy human blood, arthritic blood and arthritic synovial fluid, comparing transcriptional signatures with those from murine K/BxN serum transfer arthritis. We employed mass cytometry to quantify protein expression and sought to reproduce the synovial fluid phenotype ex vivo in cultured healthy blood neutrophils.

resultsBlood neutrophils from healthy donors and patients with active arthritis showed largely similar transcriptional signatures. By contrast, synovial fluid neutrophils exhibited more than 1600 differentially expressed genes. Gene signatures identified a prominent response to interferon gamma (IFN-γ), as well as to tumour necrosis factor, interleukin-6 and hypoxia, in both humans and mice. Mass cytometry confirmed that healthy and arthritic donor blood neutrophils are largely indistinguishable but revealed a range of neutrophil phenotypes in synovial fluid defined by downregulation of CXCR1 and upregulation of FcγRI, HLA-DR, PD-L1, ICAM-1 and CXCR4. Reproduction of key elements of this signature in cultured blood neutrophils required both IFN-γ and prolonged culture.

conclusionsCirculating neutrophils from patients with arthritis resemble those from healthy controls, but joint fluid cells exhibit a network of changes, conserved across species, that implicate IFN-γ response and ageing as complementary drivers of the synovial fluid neutrophil phenotype.

Indexed as

ArthritisNeutrophilsAgingAnimalsHumansInterferon-gammaMicePhenotypeSynovial FluidInterferon-gammaarthritisjuvenilerheumatoidsynovial fluid

Identifiers

PMID35168946
PMCPMC9380120
OpenAlexW4213321247

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.