Evidence map›Paper›PMID 34122445›Full record

ArticleFrontiers in immunology2021

NLRP3 Inflammasome Assembly in Neutrophils Is Supported by PAD4 and Promotes NETosis Under Sterile Conditions.

Patrick Münzer, Roberto Negro, Shoichi Fukui, Lucas di Meglio, Karen Aymonnier, Long Chu, Deya Cherpokova, Sarah Gutch, Nicoletta Sorvillo, Lai Shi and 6 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
128citing papers in PubMed, 3 pooled it
–field-weighted citation impact
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

128 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
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  3. Pooled it
  4. Article
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  8. HypervirulentMicrobiology spectrum · 2026
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  11. Lysosomal permeabilization by Group AInfection and immunity · 2026
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  14. From Glycocalyx Shedding to Microvascular Collapse in Sepsis: Endothelial Pathophysiology, Organ Dysfunction, and Mechanistic Biomarkers.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
    Review
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68 more citing papers are in PubMed but not listed here.

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

16 authors.

Patrick MünzerProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, United States.
Roberto NegroProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, United States.
Shoichi FukuiProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, United States.
Lucas di MeglioProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, United States.
Karen AymonnierProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, United States.
Long ChuProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, United States.
Deya CherpokovaProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, United States.
Sarah GutchProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, United States.
Nicoletta SorvilloProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, United States.
Lai ShiProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, United States.
Venkat Giri MagupalliProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, United States.
Alexander N R WeberDepartment of Immunology, Interfaculty Institute of Cell Biology, University of Tübingen, Tübingen, Germany.
Rüdiger E ScharfProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, United States.
Clare M WatermanWhitman Center, Marine Biological Laboratory, Woods Hole, MA, United States.
Hao WuProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, United States.
Denisa D WagnerProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, United States.

Funding

Mechanical Regulation of Cell AdhesionZIAHL005104 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI WATERMAN, CLARE MICHAL · 2009 to 2025
$30.9M
How inflammation and thrombosis fuel disease and aging: Focus on NETsR35HL135765 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI WAGNER, DENISA D · 2017 to 2023
$6.2M
NLRP1 and CARD8 Inflammasomes: Assembly, Regulation and Stress SensingR01AI124491 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI WU, HAO · 2016 to 2025
$5.1M
NHLBI NIH HHS R35 HL135765NIAID NIH HHS R01 AI124491
6 · The paper itself

Abstract

Neutrophil extracellular trap formation (NETosis) and the NLR family pyrin domain containing 3 (NLRP3) inflammasome assembly are associated with a similar spectrum of human disorders. While NETosis is known to be regulated by peptidylarginine deiminase 4 (PAD4), the role of the NLRP3 inflammasome in NETosis was not addressed. Here, we establish that under sterile conditions the cannonical NLRP3 inflammasome participates in NETosis. We show apoptosis-associated speck-like protein containing a CARD (ASC) speck assembly and caspase-1 cleavage in stimulated mouse neutrophils without LPS priming. PAD4 was needed for optimal NLRP3 inflammasome assembly by regulating NLRP3 and ASC protein levels post-transcriptionally. Genetic ablation of NLRP3 signaling resulted in impaired NET formation, because NLRP3 supported both nuclear envelope and plasma membrane rupture. Pharmacological inhibition of NLRP3 in either mouse or human neutrophils also diminished NETosis. Finally, NLRP3 deficiency resulted in a lower density of NETs in thrombi produced by a stenosis-induced mouse model of deep vein thrombosis. Altogether, our results indicate a PAD4-dependent formation of the NLRP3 inflammasome in neutrophils and implicate NLRP3 in NETosis under noninfectious conditions

Indexed as

AnimalsCaspase 1Disease Models, AnimalExtracellular TrapsHumansInflammasomesMaleMiceMice, Inbred C57BLMice, KnockoutNeutrophilsNLR Family, Pyrin Domain-Containing 3 ProteinProtein-Arginine Deiminase Type 4Venous ThrombosisCaspase 1InflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanNlrp3 protein, mousepeptidylarginine deiminase 4, mouseProtein-Arginine Deiminase Type 4deep vein thrombosisMCC950NETsNeutrophilsNLRP3 inflammasomePAD4

Identifiers

PMID34122445
PMCPMC8195330

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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.