Peritoneal neutrophil extracellular traps contribute to septic AKI via peritoneal IL-17A and distant organ CXCL-1/ CXCL-2 pathway in abdominal sepsis.

Yoshitaka Naito, Daiki Goto, Naoki Hayase, Xuzhen Hu, Peter S T Yuen, Robert A Star

Abstract read

In one paragraph

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

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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

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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

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

P1D6 inhibits FnBP-induced extracellular proteome remodeling: proteomic evidence for a novel intervention strategy in atopic dermatitis.Molecular medicine (Cambridge, Mass.) · 2026
Article

4 · The record

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Update of
Peritoneal Neutrophil Extracellular Traps contribute to septic AKI via peritoneal IL-17A and distant organ CXCL-1/ CXCL-2 pathway in abdominal sepsis.2025

5 · Who and what money

Authors and funding

6 authors.

Yoshitaka NaitoRenal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Building 10, Room 9N230, 10 Center Drive, MSC 1268, Bethesda, MD, 20892-1268, USA.

Daiki GotoRenal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Building 10, Room 9N230, 10 Center Drive, MSC 1268, Bethesda, MD, 20892-1268, USA.

Naoki HayaseRenal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Building 10, Room 9N230, 10 Center Drive, MSC 1268, Bethesda, MD, 20892-1268, USA.

Xuzhen HuRenal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Building 10, Room 9N230, 10 Center Drive, MSC 1268, Bethesda, MD, 20892-1268, USA.

Peter S T YuenRenal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Building 10, Room 9N230, 10 Center Drive, MSC 1268, Bethesda, MD, 20892-1268, USA. py@nih.gov.

Robert A StarRenal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Building 10, Room 9N230, 10 Center Drive, MSC 1268, Bethesda, MD, 20892-1268, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

There are no specific treatments for Sepsis-associated acute kidney injury (AKI). We previously reported that Il-17a-knockout mice had dramatically improved survival after cecal ligation and puncture (CLP). Neutrophil extracellular traps (NETs) induce IL-17A, which causes harm in some diseases, but this pathway is poorly understood in sepsis. We found that knockout of Pad4 (Peptidyl Arginine Deiminase 4), an enzyme essential for NET formation, improved survival and AKI, and suppressed neutrophil infiltration into remote organs, involving a peritoneal IL-17A/distant organ CXCL-1/CXCL-2 pathway after CLP. NETs were detected in the peritoneal cavity, and not in plasma or distant organs. Adoptive transfer of peritoneal WT neutrophils restored the IL-17A/CXCL-1/CXCL-2 pathway in Pad4KO mice, leading to neutrophil infiltration and damage to remote organs. These results revealed a pathway from peritoneal NET formation to remote organ injury/inflammation via production of IL-17A at the infectious site and distant organ CXCL-1/CXCL-2. While NETs promoted intraperitoneal IL-17A production, we also showed that conversely, peritoneal IL-17A or CXCL-1/CXCL-2 promoted intraperitoneal NET formation after CLP. This peritoneal vicious cycle that includes NET formation, IL-17A, CXCL-1/CXCL-2 that may amplify sepsis-associated organ injury. Breaking this vicious cycle by inhibiting NET formation and/or IL-17A might be a promising therapeutic target for sepsis treatment.

Indexed as

Acute Kidney InjuryChemokine CXCL1Chemokine CXCL2Extracellular TrapsInterleukin-17SepsisAnimalsDisease Models, AnimalMaleMiceMice, Inbred C57BLMice, KnockoutNeutrophil InfiltrationNeutrophilsPeritoneumProtein-Arginine Deiminase Type 4Chemokine CXCL1Chemokine CXCL2Cxcl1 protein, mouseCxcl2 protein, mouseIl17a protein, mouseInterleukin-17peptidylarginine deiminase 4, mouseProtein-Arginine Deiminase Type 4

Identifiers

PMID41588042

DOI10.1038/s41598-025-34770-1

PMCPMC12886817

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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.