Skip to content
DraconiticResearch
Search Sources API
203,234 studies31 sourcesUpdated 14 min ago
Peer-reviewedCC BY-NC-ND 4.0BMC Immunology

Neutrophil extracellular traps promote renal ischemia-reperfusion injury via a TLR2/STAT3-mediated Th17 inflammatory response

  • Yunjie Yang1,2
  • Yangyang Wu3,4
  • Xiaowei Zhang3
  • Yanpei Yang3
  • Yuandong Tao3
  • Huixia Zhou1,3
4 affiliations
  1. 1The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515 China
  2. 2Department of Pediatric Surgery, School of Medicine, the Sixth Affiliated Hospital of South China University of Technology (Nanhai District People’s Hospital of Foshan), Foshan, 528200 China
  3. 3Senior Department of Pediatrics, Chinese PLA General Hospital, Beijing, 100700 China
  4. 4Medical School of Chinese PLA, Beijing, 100700 China
Read full textDOICite

Abstract

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Although Th17 cells have been implicated in the pathogenesis of renal IRI, the mechanisms regulating Th17 responses in this context remain incompletely understood. Here, we detected abundant neutrophil extracellular traps (NETs) in kidneys following IRI. Notably, genetic ablation of Padi4 attenuated kidney injury in mice. Padi4 deficiency also reduced renal infiltration of neutrophils and macrophages. Furthermore, inhibition of NET formation by Padi4 deletion or DNase-I treatment diminished IL-17A expression and Th17 cell accumulation within IRI kidneys. Conversely, adoptive transfer of NETs elevated renal IL-17A levels and Th17 cell infiltration. Mechanistically, histones derived from NETs directly promoted Th17 differentiation via TLR2-dependent activation of intracellular STAT3 signaling. Systemic administration of histones exacerbated renal injury, kidney inflammation, and IL-17A production. Additionally, NETs-mediated Th17 responses induced CXCL1 and CXCL2 expression, thereby driving neutrophil recruitment and amplifying inflammatory cascades. Thus, our study uncovers a pathogenic loop in which NETs orchestrate Th17-driven inflammation during renal IRI.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12865-026-00889-7.

Related

  1. TH1834-Mediated TIP60 Inhibition Protects Against Ischemia/Reperfusion Damage in Human iPSC-Derived Cardiomyocytes and Cardioids
    Z. Qu, S. Murugesan, J. H. Ma +5
    bioRxivPreprintCC BY-NC-NDFull textCell biologybioRxiv
  2. A ROS-responsive platelet extracellular vesicle biomimetic nanosystem regulates CD36/Fyn-CXCL-NETosis pathway-mediated immune-inflammatory amplification in the treatment of transfusion-related acute lung injury
    Jiani Gao, Ke Zhou, Yijiu Ren +7
    Redox BiologyPeer-reviewedCC BYFull text1 citedImmunologyDOAJ
  3. RNA-binding proteome dynamics following ischemia-reperfusion injury in the kidney
    Steffen Hinrichs, Katrin Bohl, Sophie Haselhorst +14
    iSciencePeer-reviewedCC BY 4.0Systems & synthetic biologyCrossrefCell Press
  4. Regulatory roles and molecular mechanisms of N6-methyladenosine (m6A) modification in ischemia-reperfusion injury
    Di Zhang, Wenjuan An, Xing Zhang +3
    PeerJPeer-reviewedCC BY 4.0Full textGeneral biologyGeneral medicineCrossrefDOAJ
  5. Multicellular Communication Networks in Myocardial Ischemia-Reperfusion Injury: Spatial and Temporal Organization of Injury and Repair
    Yiming Wang, Yuxuan Luo
    CellsPeer-reviewedCC BY 4.0Full textCell biologyCrossrefEurope PMC

Cite

BibTeXRIS
BibTeX
@article{yang2026neutrophil,
  title = {{Neutrophil extracellular traps promote renal ischemia-reperfusion injury via a TLR2/STAT3-mediated Th17 inflammatory response}},
  author = {Yunjie Yang and Yangyang Wu and Xiaowei Zhang and Yanpei Yang and Yuandong Tao and Huixia Zhou},
  journal = {BMC Immunology},
  year = {2026},
  month = jul,
  doi = {10.1186/s12865-026-00889-7},
  url = {https://doi.org/10.1186/s12865-026-00889-7},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Neutrophil extracellular traps promote renal ischemia-reperfusion injury via a TLR2/STAT3-mediated Th17 inflammatory response
AU  - Yunjie Yang
AU  - Yangyang Wu
AU  - Xiaowei Zhang
AU  - Yanpei Yang
AU  - Yuandong Tao
AU  - Huixia Zhou
PY  - 2026
DA  - 2026/07/30
JO  - BMC Immunology
DO  - 10.1186/s12865-026-00889-7
UR  - https://doi.org/10.1186/s12865-026-00889-7
AB  - Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Although Th17 cells have been implicated in the pathogenesis of renal IRI, the mechanisms regulating Th17 responses in this context remain incompletely understood. Here, we detected abundant neutrophil extracellular traps (NETs) in kidneys following IRI. Notably, genetic ablation of Padi4 attenuated kidney injury in mice. Padi4 deficiency also reduced renal infiltration of neutrophils and macrophages. Furthermore, inhibition of NET formation by Padi4 deletion or DNase-I treatment diminished IL-17A expression and Th17 cell accumulation within IRI kidneys. Conversely, adoptive transfer of NETs elevated renal IL-17A levels and Th17 cell infiltration. Mechanistically, histones derived from NETs directly promoted Th17 differentiation via TLR2-dependent activation of intracellular STAT3 signaling. Systemic administration of histones exacerbated renal injury, kidney inflammation, and IL-17A production. Additionally, NETs-mediated Th17 responses induced CXCL1 and CXCL2 expression, thereby driving neutrophil recruitment and amplifying inflammatory cascades. Thus, our study uncovers a pathogenic loop in which NETs orchestrate Th17-driven inflammation during renal IRI.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12865-026-00889-7.
SN  - 1471-2172
ER  -