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

Abstract 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, p...

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Main Authors: 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
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Journal of Neuroinflammation
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Online Access:https://doi.org/10.1186/s12974-025-03479-3
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author 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
author_facet 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
author_sort Chenglong Liu
collection DOAJ
description Abstract 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.
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spelling doaj-art-d00a6bfca7b443bb8a8c29e457d8d3fc2025-08-20T02:30:42ZengBMCJournal of Neuroinflammation1742-20942025-06-0122112010.1186/s12974-025-03479-3Circulating T cell atlas in Moyamoya disease: insights into immunopathogenesis of cerebrovascular disordersChenglong Liu0Junsheng Li1Siqi Mou2Yuheng Pang3Liujia Chan4Qiheng He5Wei Liu6Zhikang Zhao7Bojian Zhang8Zhiyao Zheng9Wei Sun10Xiangjun Shi11Qian Zhang12Rong Wang13Yan Zhang14Wenjing Wang15Dong Zhang16Peicong Ge17Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityBeijing YouAn Hospital, Beijing Institute of Hepatology, Capital Medical UniversityDepartment of Medicinal Chemistry, College of Pharmaceutical Sciences, Capital Medical UniversityDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityChina National Clinical Research Center for Neurological DiseasesDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityBeijing YouAn Hospital, Beijing Institute of Hepatology, Capital Medical UniversityDepartment of Neurosurgery, Beijing Hospital, National Center of GerontologyDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityAbstract 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.https://doi.org/10.1186/s12974-025-03479-3Moyamoya diseaseT cellsMitochondrial dysfunctionImmunometabolismMass cytometry
spellingShingle 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
Circulating T cell atlas in Moyamoya disease: insights into immunopathogenesis of cerebrovascular disorders
Journal of Neuroinflammation
Moyamoya disease
T cells
Mitochondrial dysfunction
Immunometabolism
Mass cytometry
title Circulating T cell atlas in Moyamoya disease: insights into immunopathogenesis of cerebrovascular disorders
title_full Circulating T cell atlas in Moyamoya disease: insights into immunopathogenesis of cerebrovascular disorders
title_fullStr Circulating T cell atlas in Moyamoya disease: insights into immunopathogenesis of cerebrovascular disorders
title_full_unstemmed Circulating T cell atlas in Moyamoya disease: insights into immunopathogenesis of cerebrovascular disorders
title_short Circulating T cell atlas in Moyamoya disease: insights into immunopathogenesis of cerebrovascular disorders
title_sort circulating t cell atlas in moyamoya disease insights into immunopathogenesis of cerebrovascular disorders
topic Moyamoya disease
T cells
Mitochondrial dysfunction
Immunometabolism
Mass cytometry
url https://doi.org/10.1186/s12974-025-03479-3
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