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Background <p>Moyamoya disease (MMD) is a chronic cerebrovascular disorder characterized by progressive stenosis or occlusion of the intracranial arteries, accompanied by the formation of fragile collateral vessels, ultimately leading to ischemic or hemorrhagic strokes. Immune dysregulation, particularly involving T cell abnormalities and mitochondrial dysfunction, plays a critical role in the pathogenesis of MMD; however, their precise relationship remains unclear.</p> Methods <p>Peripheral blood mononuclear cells (PBMCs) from patients with MMD and healthy controls were analyzed using mass cytometry (CyTOF) and transcriptomic profiling. Additionally, clinical characteristics and neuroimaging data were collected to perform integrated correlation analyses with immune profiling data.</p> Results <p>Patients with MMD exhibited aberrant T cell activation and altered subset distribution, accompanied by mitochondrial dysfunction and impaired oxidative phosphorylation capacity. Increased oxidative stress and endoplasmic reticulum stress were observed in T cells, along with disease-specific downregulation of immune checkpoint molecules, including PD-1 and ICOS.</p> Conclusions <p>This study highlights the critical involvement of immune activation and mitochondrial dysfunction in the pathophysiology of MMD, providing novel insights into disease mechanisms and identifying immunometabolic pathways as potential targets for therapeutic intervention.</p>

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Circulating T cell atlas in Moyamoya disease: insights into immunopathogenesis of cerebrovascular disorders

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月5日

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  • Chenglong Liu,
  • Junsheng Li,
  • Siqi Mou,
  • Yuheng Pang,
  • Liujia Chan,
  • Qiheng He,
  • Wei Liu,
  • Zhikang Zhao,
  • Bojian Zhang,
  • Zhiyao Zheng,
  • Wei Sun,
  • Xiangjun Shi,
  • Qian Zhang,
  • Rong Wang,
  • Yan Zhang,
  • Wenjing Wang,
  • Dong Zhang,
  • Peicong Ge

摘要

Background

Moyamoya disease (MMD) is a chronic cerebrovascular disorder characterized by progressive stenosis or occlusion of the intracranial arteries, accompanied by the formation of fragile collateral vessels, ultimately leading to ischemic or hemorrhagic strokes. Immune dysregulation, particularly involving T cell abnormalities and mitochondrial dysfunction, plays a critical role in the pathogenesis of MMD; however, their precise relationship remains unclear.

Methods

Peripheral blood mononuclear cells (PBMCs) from patients with MMD and healthy controls were analyzed using mass cytometry (CyTOF) and transcriptomic profiling. Additionally, clinical characteristics and neuroimaging data were collected to perform integrated correlation analyses with immune profiling data.

Results

Patients with MMD exhibited aberrant T cell activation and altered subset distribution, accompanied by mitochondrial dysfunction and impaired oxidative phosphorylation capacity. Increased oxidative stress and endoplasmic reticulum stress were observed in T cells, along with disease-specific downregulation of immune checkpoint molecules, including PD-1 and ICOS.

Conclusions

This study highlights the critical involvement of immune activation and mitochondrial dysfunction in the pathophysiology of MMD, providing novel insights into disease mechanisms and identifying immunometabolic pathways as potential targets for therapeutic intervention.