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Updated: Jul 11, 2026
07:05
Visualization of Neutrophil Extracellular Traps in Mesenteric Venules After Mesenteric Ischemia-Reperfusion Injury via Intravital Microscopy
Published on: September 27, 2024
946
IL-17A Promotes NETs Formation via the PKCζ-ERK-ROS-PAD4 Pathway in a Mouse Model of Ischemic Stroke
Chang Liu1, Qi Chen1, Weijia Chen1
1Department of Geriatrics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
CNS Neuroscience & Therapeutics
|March 10, 2026
Summary
Interleukin-17A (IL-17A) worsens stroke damage by increasing neutrophil extracellular traps (NETs) via PAD4. Targeting the PKCζ-ERK-ROS pathway offers a potential new stroke therapy.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Interleukin-17A (IL-17A) is known to worsen neurological damage after stroke.
- IL-17A also enhances neutrophil extracellular traps (NETs) formation, but the mechanism is not fully understood.
Purpose of the Study:
- To elucidate the mechanism by which IL-17A regulates NETs generation after ischemic stroke.
- To investigate the role of Peptidylarginine deiminase 4 (PAD4) in IL-17A-mediated NETs formation.
Main Methods:
- A mouse middle cerebral artery occlusion (MCAO) model was used.
- Mice were treated with a PAD4 inhibitor (GSK484) or an IL-17A-neutralizing antibody (IL-17mAb).
- Infarct volume, neurological function, and protein expression (PAD4, MPO, CitH3, PKCζ, p-ERK) were assessed. IL-17A knockout mice and primary neutrophils were also used.
Main Results:
- Inhibition of PAD4 reduced infarct size and improved neurological outcomes.
- IL-17mAb treatment decreased PAD4, MPO, CitH3, PKCζ, and p-ERK expression.
- IL-17A knockout mice showed reduced PAD4 and CitH3 expression in the peri-infarct area.
- In vitro studies confirmed IL-17A upregulates PAD4 via the PKCζ-ERK-ROS axis.
Conclusions:
- IL-17A promotes NETs formation by upregulating PAD4 through the PKCζ-ERK-ROS pathway, exacerbating ischemic brain injury.
- Targeting the IL-17A-PAD4 axis presents a potential therapeutic strategy for stroke.
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