Evidence map›Paper›PMID 33983685›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2021

RNA Externalized by Neutrophil Extracellular Traps Promotes Inflammatory Pathways in Endothelial Cells.

Luz P Blanco, Xinghao Wang, Philip M Carlucci, Jose Jiram Torres-Ruiz, Jorge Romo-Tena, Hong-Wei Sun, Markus Hafner, Mariana J Kaplan

Open access · greenAbstract read
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 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
3.3field-weighted citation impact, top 7% 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, 60 citations in OpenAlex.

  1. Review
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  8. Article
  9. Immunometabolism in systemic lupus erythematosus.Nature reviews. Rheumatology · 2025
    Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Neutrophil extracellular traps in homeostasis and disease.Signal transduction and targeted therapy · 2024
    Review
  19. Article
  20. Vascular damage in systemic lupus erythematosus.Nature reviews. Nephrology · 2024
    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

8 authors at 1 institution in 2 countries.

Luz P BlancoNational Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland.ORCID 0000-0002-8468-6518
Xinghao WangNational Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland.ORCID 0000-0001-8264-8537
Philip M CarlucciNational Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland.ORCID 0000-0002-9729-4572
Jose Jiram Torres-RuizNational Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland.
Jorge Romo-TenaNational Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, and Universidad Nacional Autónoma de México, Mexico City, Mexico.
Hong-Wei SunNational Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland.
Markus HafnerNational Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland.
Mariana J KaplanNational Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland.ORCID 0000-0003-2968-0815
National Institute of Arthritis and Musculoskeletal and Skin Diseases · US

Funding

Systemic AutoimmunityZIAAR041199 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI KAPLAN, MARIANA · 2014 to 2025
$32.5M
Applying Bioinformatics to Research in Immune, Muscle, and Bone DiseasesZICAR041173 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI SUN, HONG-WEI · 2021 to 2025
$10.3M
Integration of the results from systems-level determination of cis-acting elements into high-resolution maps of posttranscriptional regulatory events.ZIAAR041205 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI HAFNER, MARKUS · 2016 to 2025
$5.5M
Intramural NIH HHS ZIA AR041199NIAMS NIH HHS ZIAAR041199
6 · The paper itself

Abstract

objectiveNeutrophil extracellular traps (NETs) are extracellular lattices composed of nucleic material bound to neutrophil granule proteins. NETs may play pathogenic roles in the development and severity of autoimmune diseases such as systemic lupus erythematosus (SLE), at least in part, through induction of type I interferon (IFN) responses via externalization of oxidized immunostimulatory DNA. A distinct subset of SLE proinflammatory neutrophils (low-density granulocytes [LDGs]) displays enhanced ability to form proinflammatory NETs that damage the vasculature. We undertook this study to assess whether NET-bound RNA can contribute to inflammatory responses in endothelial cells (ECs) and the pathways that mediate this effect.

methodsExpression of newly synthesized and total RNA was quantified in NETs from healthy controls and lupus patients. The ability of ECs to take up NET-bound RNA and downstream induction of type I IFN responses were quantified. RNAs present in NETs were sequenced and specific small RNAs were tested for induction of endothelial type I IFN pathways.

resultsNETs extruded RNA that was internalized by ECs, and this was enhanced when NET-bound nucleic acids were oxidized, particularly in lupus LDG-derived NETs. Internalization of NET-bound RNA by ECs was dependent on endosomal Toll-like receptors (TLRs) and the actin cytoskeleton and induced type I IFN-stimulated genes (ISGs). This ISG induction was dependent on NET-associated microRNA let-7b, a small RNA expressed at higher levels in LDG-derived NETs, which acted as a TLR-7 agonist.

conclusionThese findings highlight underappreciated roles for small RNAs externalized in NETs in the induction of proinflammatory responses in vascular cells, with implications for lupus vasculopathy.

Indexed as

AortaCell LineEndothelial CellsExtracellular TrapsHumansInflammationLupus Erythematosus, SystemicMicroRNAsNeutrophilsMicroRNAs

Identifiers

PMID33983685
PMCPMC8589882
OpenAlexW3161169825

What OpenQuestion holds

Textmetadata
LicenceTDM
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.