SELL Marks an Effector-Deficient CD8⁺ T Cell Subset That Promotes Intracerebral Hemorrhage and Responds to Rutin...

Area of Science:

• Immunology
• Neuroscience
• Genomics

Background:

• Intracerebral hemorrhage (ICH) is a severe stroke with high mortality and few treatments.
• Neuroinflammation worsens secondary brain injury after ICH.
• The role of peripheral CD8+ T cell dysfunction in ICH is not well understood.

Purpose of the Study:

• Identify CD8+ T cell subpopulations linked to ICH.
• Discover potential therapeutic targets for ICH.
• Investigate the role of peripheral immune cells in ICH pathogenesis.

Main Methods:

• Integrated bulk and single-cell RNA sequencing from ICH patients and controls.
• Applied machine learning algorithms for biomarker discovery.
• Evaluated rutin's efficacy in murine ICH models.

Main Results:

• Identified a SELL-high CD8+ T cell subpopulation with impaired cytotoxicity.
• SELL was validated as a reliable diagnostic biomarker for ICH (AUC: 0.876-0.936).
• Rutin treatment improved CD8+ T cell function, reduced hemorrhage, and mitigated neuroinflammation in mice.

Conclusions:

• Effector-deficient, SELL-marked CD8+ T cells are a hallmark of ICH.
• SELL is a robust diagnostic biomarker for ICH.
• Rutin is a potential therapeutic agent for hypertensive ICH targeting peripheral immune dysfunction.