Multi-Omics Insights Into Circulating T-Cell Metabolic Reprogramming and Treg Dysfunction in Moyamoya Disease.
8 affiliations
- 1Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing China.
- 2Basic and Translational Medicine Center National Clinical Research Center for Neurological Diseases Beijing Tiantan Hospital Capital Medical University Beijing China.
- 3Research Unit of Accurate Diagnosis Treatment, and Translational Medicine of Brain Tumors Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China.
- 4Department of Neurosurgery Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China.
- 5Department of Rheumatology and Immunology Beijing Tiantan Hospital Capital Medical University Beijing China.
- 6Beijing Institute of Hepatology Beijing Youan Hospital Capital Medical University Beijing China.
- 7Department of Neurosurgery Beijing Hospital National Center of Gerontology Beijing China.
- 8Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing China.
Abstract
Moyamoya disease (MMD) is a progressive cerebrovascular disease linked to immune dysregulation, yet T-cell metabolic reprogramming and regulatory T-cell (Treg) function remain poorly understood. Here, we integrated multi-omics approaches, including mass cytometry, single-cell RNA sequencing, bulk RNA sequencing, metabolomics, and flow cytometry to characterize T-cell metabolic alterations and Treg dysfunction in MMD, uncovering a key metabolic-immune axis. Compared with healthy controls, MMD patients showed chronic immune activation and broad suppression of amino acid, glycolytic, and fatty acid metabolic pathways. Although Tregs were aberrantly expanded, they displayed metabolic inflexibility, together with impaired intercellular communication. Single-cell transcriptomics indicated Treg-to-Th17 conversion, while flow cytometry confirmed increased IL-17A⁺ cells within the CD4⁺FOXP3⁺ compartment. Besides, these dysfunctional Tregs correlated with advanced Suzuki stages, ischemic stroke, and posterior cerebral artery involvement. Bulk transcriptomic and serum metabolomic analyses further confirmed coordinated immune activation and metabolic suppression at the gene, protein, pathway, and metabolite levels. These findings define a metabolic-immune axis in MMD in which metabolically constrained, functionally unstable Tregs may contribute to neuroinflammation and vascular remodeling, suggesting that restoring Treg metabolic fitness could represent a therapeutic strategy.
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BibTeX
@article{zheng2026multiomics,
title = {{Multi-Omics Insights Into Circulating T-Cell Metabolic Reprogramming and Treg Dysfunction in Moyamoya Disease.}},
author = {Zhiyao Zheng and Qiheng He and Xinyu Ma and Bojian Zhang and Junsheng Li and Chenglong Liu and Siqi Mou and Wei Sun and Xiangjun Shi and Wenjing Wang and Dong Zhang and Peicong Ge and Jizong Zhao},
journal = {MedComm},
year = {2026},
month = oct,
doi = {10.1002/mco2.71088},
url = {https://europepmc.org/article/MED/42921569},
note = {CC BY},
}
RIS
TY - JOUR
TI - Multi-Omics Insights Into Circulating T-Cell Metabolic Reprogramming and Treg Dysfunction in Moyamoya Disease.
AU - Zhiyao Zheng
AU - Qiheng He
AU - Xinyu Ma
AU - Bojian Zhang
AU - Junsheng Li
AU - Chenglong Liu
AU - Siqi Mou
AU - Wei Sun
AU - Xiangjun Shi
AU - Wenjing Wang
AU - Dong Zhang
AU - Peicong Ge
AU - Jizong Zhao
PY - 2026
DA - 2026/10/23
JO - MedComm
DO - 10.1002/mco2.71088
UR - https://europepmc.org/article/MED/42921569
AB - Moyamoya disease (MMD) is a progressive cerebrovascular disease linked to immune dysregulation, yet T-cell metabolic reprogramming and regulatory T-cell (Treg) function remain poorly understood. Here, we integrated multi-omics approaches, including mass cytometry, single-cell RNA sequencing, bulk RNA sequencing, metabolomics, and flow cytometry to characterize T-cell metabolic alterations and Treg dysfunction in MMD, uncovering a key metabolic-immune axis. Compared with healthy controls, MMD patients showed chronic immune activation and broad suppression of amino acid, glycolytic, and fatty acid metabolic pathways. Although Tregs were aberrantly expanded, they displayed metabolic inflexibility, together with impaired intercellular communication. Single-cell transcriptomics indicated Treg-to-Th17 conversion, while flow cytometry confirmed increased IL-17A⁺ cells within the CD4⁺FOXP3⁺ compartment. Besides, these dysfunctional Tregs correlated with advanced Suzuki stages, ischemic stroke, and posterior cerebral artery involvement. Bulk transcriptomic and serum metabolomic analyses further confirmed coordinated immune activation and metabolic suppression at the gene, protein, pathway, and metabolite levels. These findings define a metabolic-immune axis in MMD in which metabolically constrained, functionally unstable Tregs may contribute to neuroinflammation and vascular remodeling, suggesting that restoring Treg metabolic fitness could represent a therapeutic strategy.
SN - 2688-2663
ER -