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Association of increased Treg and Th17 with pathogenesis of moyamoya disease
Leihua Weng1,2, Xiang Cao1,3, Lijuan Han1,3
1Department of Neurology and Neurosurgery, Drum Tower Hospital of Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, P. R. China.
Abstract:
Immuno-inflammation has been shown to play a pivotal role in the pathogenesis of moyamoya disease (MMD). However, how did circulating Treg/Th17 cells involve in MMD patients remains unclear. 26 MMD, 21 atherothrombotic stroke, and 32 healthy controls were enrolled in this study. MMD patients have a significantly higher percentage of circulating Treg and Th17 cells as well as their dominantly secreting cytokines than other groups (P < 0.0001), whereas no difference was found in the ratio of Treg/Th17 between patients in MMD and atherothrombotic stroke group or control subjects (P = 0.244). However, the increased Treg in MMD patients which were enriched with FrIII Treg cells had deficient suppressive functions (P = 0.0017) compared to healthy volunteers. There was a positive correlation between Treg or TGF-β and MMD Suzuki's stage. And the level of circulating Treg was as an independent factor associated with MMD stage. Besides, TGF-β was also correlated with the increased expression of VEGF in MMD patients. Our findings indicated an important involvement of circulating Treg in the pathogenic development of MMD and TGF-β in Treg induced VEGF.
Insights
Circulating regulatory T (Treg) cells are implicated in moyamoya disease (MMD) pathogenesis. Despite increased numbers, MMD Treg cells exhibit reduced suppressive function, correlating with disease severity and VEGF expression.
Area of Science:
- Immunology
- Neurology
- Vascular Biology
Background:
- Immuno-inflammation is key in moyamoya disease (MMD) pathogenesis.
- The specific role of circulating regulatory T (Treg) and T helper 17 (Th17) cells in MMD is not fully understood.
Purpose of the Study:
- To investigate the involvement of circulating Treg and Th17 cells in MMD.
- To analyze the functional capacity of Treg cells and their correlation with disease severity and molecular markers in MMD patients.
Main Methods:
- Comparative analysis of Treg and Th17 cell percentages and cytokine profiles in MMD patients, atherothrombotic stroke patients, and healthy controls.
- Assessment of Treg cell suppressive function and correlation analysis with MMD Suzuki stage, TGF-β, and VEGF levels.
Main Results:
- MMD patients showed significantly higher percentages of circulating Treg and Th17 cells and their associated cytokines compared to controls.
- Increased Treg cells in MMD patients, particularly FrIII Treg cells, exhibited deficient suppressive functions.
- A positive correlation was observed between Treg cells, TGF-β, and MMD Suzuki stage; circulating Treg levels independently predicted MMD stage.
- TGF-β levels correlated with increased VEGF expression in MMD patients.
Conclusions:
- Circulating Treg cells play a significant role in the pathogenic development of MMD.
- TGF-β contributes to Treg-induced VEGF upregulation in MMD, highlighting potential therapeutic targets.
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