Inhibition of NETosis by a Nuclear-Penetrating Anti-DNA Autoantibody
Xiaoyong Chen1, Benedette J Cuffari1, Valentina Dubljevic2
1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT.
Immunohorizons
|June 13, 2022
Summary
Nuclear-penetrating anti-DNA autoantibodies can suppress neutrophil extracellular trap (NET) release by interfering with DNA repair. This discovery offers potential therapeutic strategies for diseases involving NETosis.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Nuclear-penetrating anti-DNA autoantibodies show promise for targeted therapies.
- Neutrophil extracellular traps (NETs) and NETosis are implicated in various diseases.
- The DNA damage response (DDR) is linked to NETosis mechanisms.
Purpose of the Study:
- To evaluate the impact of a nuclear-penetrating anti-DNA autoantibody on NETosis.
- To determine if this autoantibody can inhibit DNA and NET release from activated neutrophils.
Main Methods:
- Utilized differentiated PLB-985 cells and mouse neutrophils.
- Stimulated NETosis using PMA and ionomycin.
- Assessed NETosis via DNA staining, DNA release measurements, Western blot for histone citrullination, and confocal microscopy.
Main Results:
- Autoantibody treatment significantly inhibited both NADPH oxidase-dependent and independent NETosis.
- Demonstrated suppression of DNA decondensation and NET release.
Conclusions:
- Nuclear-penetrating anti-DNA autoantibodies can modulate neutrophil function.
- These autoantibodies represent a potential therapeutic strategy to suppress NETosis.
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