RAD51 stabilizes neutrophil extracellular traps to compartmentalize inflammation

Neutrophil extracellular traps (NETs) feature a branched chromatin architecture whose origin and function remain unknown. We found that NET branching is mediated by RAD51, a protein generating DNA junctions during DNA recombination repair. Pharmacological inhibition, RAD51 knockdown, or GEN1 and RuvC resolvase treatment reduced branching and destabilized NETs, whereas RAD51 up-regulation by different stimuli generated NETs with variable stability. RAD51 inhibition during murine pulmonary Aspergillus fumigatus infection dismantled NETs and reduced lung cytokines. However, the increased accumulation of NET components in the circulation led to interleukin-6 (IL-6) induction in circulating monocytes that exacerbated type 2 inflammation and asthma. Extracellular plasma DNA correlated with IL-6 and eotaxin in human aspergillosis. By structurally stabilizing NETs, RAD51 compartmentalizes inflammation to thwart aberrant systemic immune activation, linking DNA repair to inflammation.

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Publication Details

Journal
Science
Published
2026-08-20
DOI
https://doi.org/10.1126/science.aed9286
Primary Topic
Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Type
article
Field-Weighted Citation Impact
0.00

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article

RAD51 stabilizes neutrophil extracellular traps to compartmentalize inflammation

Darius P. H. Armstrong-James, Venizelos Papayannopoulos, Thomas J Williams, Stephen C. West et al.
Science
Neutrophil, Myeloperoxidase and Oxidative Mechanisms
article

RAD51 stabilizes neutrophil extracellular traps to compartmentalize inflammation

Darius P. H. Armstrong-James, Venizelos Papayannopoulos, Thomas J Williams, Stephen C. West, Iker Valle Aramburu, Lorenza Iolanda Tsansizi, Rajvee Shah Punatar, Anna Reed, Yihe E. Qiao, Sophie Yihan Guan
article en

Abstract

Neutrophil extracellular traps (NETs) feature a branched chromatin architecture whose origin and function remain unknown. We found that NET branching is mediated by RAD51, a protein generating DNA junctions during DNA recombination repair. Pharmacological inhibition, RAD51 knockdown, or GEN1 and RuvC resolvase treatment reduced branching and destabilized NETs, whereas RAD51 up-regulation by different stimuli generated NETs with variable stability. RAD51 inhibition during murine pulmonary Aspergillus fumigatus infection dismantled NETs and reduced lung cytokines. However, the increased accumulation of NET components in the circulation led to interleukin-6 (IL-6) induction in circulating monocytes that exacerbated type 2 inflammation and asthma. Extracellular plasma DNA correlated with IL-6 and eotaxin in human aspergillosis. By structurally stabilizing NETs, RAD51 compartmentalizes inflammation to thwart aberrant systemic immune activation, linking DNA repair to inflammation.

ScienceVol. 393(6813)
Guy's and St Thomas' NHS Foundation Trust (GB), Royal Brompton & Harefield NHS Foundation Trust (GB), The Francis Crick Institute (GB), Harefield Hospital (GB), Imperial College London (GB)
Wellcome Trust, Francis Crick Institute, Louis-Jeantet Foundation, Biotechnology and Biological Sciences Research Council
Good health and well-being
Openalex Percentile: Top 16%
Neutrophil, Myeloperoxidase and Oxidative Mechanisms
DOIOpen Access PDFOpenAlex
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