Evidence map›Paper›PMID 32597834›Full record

ArticleThe Journal of clinical investigation2020

Epithelial-derived gasdermin D mediates nonlytic IL-1β release during experimental colitis.

Katarzyna Bulek, Junjie Zhao, Yun Liao, Nitish Rana, Daniele Corridoni, Agne Antanaviciute, Xing Chen, Han Wang, Wen Qian, William A Miller-Little and 10 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
149citing papers in PubMed, 2 pooled it
8.1field-weighted citation impact, top 2% 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

149 citing papers in PubMed, 2 syntheses or guidelines pooled it, 150 citations in OpenAlex.

  1. Pooled it
  2. Review: the role of GSDMD in sepsis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022
    Pooled it
  3. The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026
    Review
  4. Article
  5. Review
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  7. Temporal transcriptomic profiling identifies core regulators in cytokine-induced gut barrier disruption in differentiated Caco-2 cells.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
  8. Review
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  13. Review
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  20. De novo discovery of bicyclic cysteine-rich peptides targeting gasdermin D.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article

89 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

20 authors at 5 institutions in 3 countries.

Katarzyna BulekDepartment of Inflammation and Immunity, Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio, USA.
Junjie ZhaoDepartment of Inflammation and Immunity, Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio, USA.
Yun LiaoDepartment of Inflammation and Immunity, Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio, USA.
Nitish RanaDepartment of Pathology and.
Daniele CorridoniMedical Research Counsel (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
Agne AntanaviciuteMedical Research Counsel (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
Xing ChenDepartment of Inflammation and Immunity, Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio, USA.
Han WangDepartment of Inflammation and Immunity, Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio, USA.
Wen QianDepartment of Inflammation and Immunity, Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio, USA.
William A Miller-LittleDepartment of Inflammation and Immunity, Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio, USA.
Shadi SwaidaniDepartment of Cardiovascular and Metabolic Sciences and.
Fangqiang TangDepartment of Inflammation and Immunity, Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio, USA.
Belinda B WillardProteomics and Metabolomics Core, Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio, USA.
Keith McCraeDepartment of Cardiovascular and Metabolic Sciences and.
Zizhen KangDepartment of Inflammation and Immunity, Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio, USA.
George R DubyakDepartment of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Fabio CominelliDepartment of Pathology and.
Alison SimmonsMedical Research Counsel (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
Theresa T PizarroDepartment of Pathology and.
Xiaoxia LiDepartment of Inflammation and Immunity, Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio, USA.
Cleveland Clinic Lerner College of Medicine · USMRC Human Immunology Unit · GBUniversity School · USJagiellonian University · PLUniversity Hospitals of Cleveland · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
Vascular Cell function and AtherosclerosisP01HL029582 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI FOX, PAUL L · 1985 to 2019
$32.0M
Targeting pathological hyaluronan matricesP01HL103453 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI REIZES, OFER · 2011 to 2020
$26.8M
Ubiquitination Pathways Mediating Chronic Intestinal InflammationP01DK091222 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI COMINELLI, FABIO · 2011 to 2020
$16.5M
The Cleveland Digestive Diseases Research Core Center (DDRCC)P30DK097948 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI Theresa Torres Pizarro · 2015 to 2026
$15.6M
MECHANISMS OF EXPERIMENTAL CROHNS DISEASER01DK055812 · NIDDK · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI COMINELLI, FABIO · 1999 to 2019
$4.9M
CYTOKINES AND INFLAMMATORY BOWEL DISEASER01DK042191 · NIDDK · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI COMINELLI, FABIO, PIZARRO, THERESA TORRES · 1995 to 2022
$4.7M
THE INTEGRATION OF IL-17 AND NOTCH SIGNALING IN THE PATHOGENESIS OF CNS INFLAMMATIONR01NS104164 · NINDS · UNIVERSITY OF IOWA · PI KANG, ZIZHEN · 2018 to 2022
$1.7M
High-End Instrumentation (HEI) Grant Program (S10)S10OD023436 · OD · CLEVELAND CLINIC LERNER COM-CWRU · PI WILLARD, BELINDA BELLE · 2017 to 2017
$873k
LTQ-Orbitrap Velos instrumentS10RR031537 · NCRR · CLEVELAND CLINIC LERNER COM-CWRU · PI WILLARD, BELINDA BELLE · 2011 to 2011
$600k
Medical Research Council MC_PC_MR/S025952/1Medical Research Council MC_UU_00008/7Medical Research Council MC_UU_12010/7Medical Research Council MR/S036377/1NCRR NIH HHS S10 RR031537NHLBI NIH HHS P01 HL029582NHLBI NIH HHS P01 HL103453NIDDK NIH HHS P01 DK091222NIDDK NIH HHS P30 DK097948NIDDK NIH HHS R01 DK042191NIDDK NIH HHS R01 DK055812NIGMS NIH HHS T32 GM007250NIH HHS S10 OD023436NINDS NIH HHS R01 NS104164
6 · The paper itself

Abstract

Gasdermin D (GSDMD) induces pyroptosis via the pore-forming activity of its N-terminal domain, cleaved by activated caspases associated with the release of IL-1β. Here, we report a nonpyroptotic role of full-length GSDMD in guiding the release of IL-1β-containing small extracellular vesicles (sEVs) from intestinal epithelial cells (IECs). In response to caspase-8 inflammasome activation, GSDMD, chaperoned by Cdc37/Hsp90, recruits the E3 ligase, NEDD4, to catalyze polyubiquitination of pro-IL-1β, serving as a signal for cargo loading into secretory vesicles. GSDMD and IL-1β colocalize with the exosome markers CD63 and ALIX intracellularly, and GSDMD and NEDD4 are required for release of CD63+ sEVs containing IL-1β, GSDMD, NEDD4, and caspase-8. Importantly, increased expression of epithelial-derived GSDMD is observed both in patients with inflammatory bowel disease (IBD) and those with experimental colitis. While GSDMD-dependent release of IL-1β-containing sEVs is detected in cultured colonic explants from colitic mice, GSDMD deficiency substantially attenuates disease severity, implicating GSDMD-mediated release of IL-1β sEVs in the pathogenesis of intestinal inflammation, such as that observed in IBD.

Indexed as

AnimalsCell LineColitisEpithelial CellsExosomesExtracellular VesiclesGasderminsInflammatory Bowel DiseasesInterleukin-1betaIntestinal MucosaIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutNedd4 Ubiquitin Protein LigasesPhosphate-Binding ProteinsTetraspanin 30Cd63 protein, mouseGasderminsGsdmd protein, mouseIL1B protein, mouseInterleukin-1betaIntracellular Signaling Peptides and ProteinsNedd4 protein, mouseNedd4 Ubiquitin Protein LigasesPhosphate-Binding ProteinsTetraspanin 30CytokinesGastroenterologyInflammationInflammatory bowel diseaseInnate immunity

Identifiers

PMID32597834
PMCPMC7410065
OpenAlexW3037924264

What OpenQuestion holds

Textmetadata
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.