Evidence mapPaperPMID 41557019Full record

ArticleInflammation2026

Interleukin-33 Promotes Neutrophil Extracellular Trap Formation To Aggravate Renal Ischemia-Reperfusion Injury Through ST2/PI3K/Akt and ST2/PAD4 Pathways.

Feilong Zhang, Jiyue Wu, Zhen Li, Lijian Gan, Haoyuan Cao, Chaozhen Chen, Zejia Sun, Jiandong Zhang, Hailong Li, Xulong Zhang and 1 more

Abstract read
In one paragraph

Article in Inflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
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

1 citing paper in PubMed.

  1. 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

11 authors.

Feilong Zhang *Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Jiyue Wu *Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Zhen Li *Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Lijian GanDepartment of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Haoyuan CaoDepartment of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Chaozhen ChenDepartment of Urology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Zejia SunDepartment of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Jiandong ZhangDepartment of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Hailong LiDepartment of Urology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. justinlee719@163.com.
Xulong ZhangDepartment of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China. zhxlwl@hotmail.com.
Wei WangDepartment of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China. weiwang0920@163.com.

Funding

Beijing Municipal Science and Technology Commission Z221100007422029Clinical Research Incubation Project of Beijing Chao-Yang Hospital, Capital Medical University CYFH202203Golden Seed Research Grant Project of Beijing Chao-Yang Hospital, Capital Medical University CYJZ202521National Natural Science Foundation of China 82370752
6 · The paper itself

Abstract

Renal ischemia-reperfusion injury (IRI) triggers a sterile immune response, primarily mediated by the innate immune system. Interleukin-33 (IL-33) promotes neutrophil infiltration during inflammatory processes, and neutrophils play a critical role in renal IRI pathology. This study aims to elucidate the mechanisms of IL-33 in neutrophil extracellular trap (NET) formation during renal IRI. The association between IL-33 and NET formation was investigated using suppression of tumorigenicity 2 (ST2) knockout (KO) mice, RNA sequencing, and pharmacological interventions. Results revealed that compared with preoperative levels, postoperative serum IL-33 and NET formation were elevated and positively correlated in patients undergoing renal transplantation. Similarly, the mouse model of renal I/R exhibited increased IL-33 expression and NET formation, which were also highly correlated. Administration of recombinant IL-33 during renal I/R enhanced NET formation and worsened renal IRI. However, treatment with an anti-IL-33 monoclonal antibody decreased NET formation and mitigated renal IRI. ST2 KO mice exhibited reduced NET formation and increased protection against renal IRI compared to control mice after renal I/R. In vitro studies showed that IL-33 dose-dependently promoted NET formation in neutrophils. Mechanistically, IL-33-induced NET formation was markedly reduced in ST2 KO mouse-derived neutrophils. Furthermore, RNA sequencing results revealed that IL-33-induced NET formation was mediated via ST2/ PI3K/Akt and ST2/peptidylarginine deiminase 4 (PAD4) signaling pathways. Inhibition of these pathways significantly suppressed IL-33-induced NET formation. In summary, this study demonstrates that IL-33/ST2 signaling exacerbates renal IRI by amplifying NETs. Targeting the IL-33/ST2 axis and inhibiting NET formation offers promising therapeutic strategies for preventing and treating renal IRI.

Indexed as

Extracellular TrapsInterleukin-1 Receptor-Like 1 ProteinInterleukin-33KidneyProtein-Arginine Deiminase Type 4Proto-Oncogene Proteins c-aktReperfusion InjuryAnimalsHumansKidney TransplantationMaleMiceMice, Inbred C57BLMice, KnockoutNeutrophilsPhosphatidylinositol 3-KinasesIL1RL1 protein, humanIl1rl1 protein, mouseIl33 protein, mouseInterleukin-1 Receptor-Like 1 ProteinInterleukin-33peptidylarginine deiminase 4, mousePhosphatidylinositol 3-KinasesProtein-Arginine Deiminase Type 4Proto-Oncogene Proteins c-aktIL-33IRINETsNeutrophil extracellular trapRenal ischemia-reperfusion injuryST2

Identifiers

PMID41557019
PMCPMC12882866

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.