Double-negative T cells remarkably promote neuroinflammation after ischemic stroke

Area of Science:

• Neuroimmunology
• Immunology
• Stroke Research

Background:

• Double-negative T cells (DNTs) regulate immune homeostasis in peripheral diseases.
• The role of DNTs in the central nervous system, particularly during stroke, is not well understood.

Purpose of the Study:

• To investigate the function and impact of DNTs in the central nervous system following ischemic stroke.
• To explore DNTs as a potential therapeutic target for stroke treatment.

Main Methods:

• Quantification of DNT levels in the brain and blood of stroke patients and a mouse model.
• Analysis of the molecular pathways modulated by DNTs in ischemic brain injury.
• Evaluation of therapeutic blockade of the FasL/PTPN2/TNF-α pathway in a mouse stroke model.

Main Results:

• DNT levels significantly increased in the brain and blood during stroke in a time-dependent manner.
• Infiltrating DNTs exacerbated ischemic brain injury by enhancing neuroinflammation via the FasL/PTPN2/TNF-α pathway.
• Blocking this pathway reduced DNT-mediated neuroinflammation and improved stroke outcomes in mice.

Conclusions:

• DNTs play a critical role in exacerbating ischemic brain injury by promoting neuroinflammation.
• Targeting the FasL/PTPN2/TNF-α pathway offers a promising therapeutic strategy for stroke.
• DNTs represent a novel and attractive target for treating ischemic stroke.