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.
Highlights
Moyamoya disease (MMD) is a chronic steno-occlusive cerebrovascular disorder characterized by progressive stenosis of the terminal internal carotid artery (ICA) and/or its proximal branches, typically accompanied by an abnormally thin and fragile collateral vascular network at the base of the brain developed to compensate as the blood flow decreases in the affected area[1]
There was no significant difference in leukocyte count and C-reactive protein (CRP)levels among MMD, atherothrombotic stroke and controls
The serum protein level of several inflammatory molecules including HMGB-1, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM) in MMD patients was strikingly increased by 92.32% [57.000 (34.000, 154.000) vs. 27.000 (13.500, 61.000), P < 0.05], 31.66% [38.070 (31.750, 42.760) vs. 28.080 (21.280, 34.905), P < 0.01] and 51.5% [158.135 (130.560, 211.360) vs. 103.975 (85.435, 135.810), P < 0.001], respectively. (Supplementary Fig. 1) These findings indicate that peripheral inflammatory responses were induced in MMD patients
Summary
Moyamoya disease (MMD) is a chronic steno-occlusive cerebrovascular disorder characterized by progressive stenosis of the terminal internal carotid artery (ICA) and/or its proximal branches, typically accompanied by an abnormally thin and fragile collateral vascular network at the base of the brain developed to compensate as the blood flow decreases in the affected area[1]. Imbalance of two unique CD4+T helper (Th) cell subsets, Treg and Th17 cells, has been implicated in the pathogenesis of a wide spectrum of autoimmune and inflammatory diseases[5, 6]. Whether Treg/Th17 cells are involved in the pathogenic development of MMD remains to be explored. Treg-produced transforming growth factor (TGF)-β1 could induce production of VEGF and stimulate subsequent angiogenesis[12]. Whether Treg/Th17 contribute to the production of VEGF and subsequent angiogenesis in development of MMD was unknown. We would like to investigate here whether imbalance of Treg/Th17 is associated with the course of MMD, and if so whether it contributes to abnormal angiogenesis in MMD through regulation of VEGF signaling. Our results will clarify the importance of Treg/Th17s in the pathogenesis of MMD, providing a potential therapeutic target for MMD patients
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