RAD51 stabilizes neutrophil extracellular traps to compartmentalize inflammation.
basic_science · Level V
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- Record sourced from PubMed, PMID 42623469.
- Also identified by DOI 10.1126/science.aed9286.
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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, <i>RAD51</i> 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 <i>Aspergillus fumigatus</i> 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.
Medical subject headings
- Extracellular Traps
- Rad51 Recombinase
- Neutrophils
- Inflammation