RAD51 stabilizes neutrophil extracellular traps to compartmentalize inflammation.
RAD51 is important for stabilizing neutrophil extracellular traps, which may help manage inflammation, but the implications for human health need further investigation.
Where it sits
this study against the rest of the ll-37 corpusSummary and findings
This study examined the role of RAD51 in the stability of neutrophil extracellular traps (NETs) and its implications for inflammation. In murine models, RAD51 inhibition during pulmonary Aspergillus fumigatus infection reduced lung cytokines and destabilized NETs. The study also found correlations between extracellular plasma DNA and IL-6 in human aspergillosis.
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.
Background
Not reported in abstract.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Not reported in abstract.
Limitations
Not reported in abstract.