Association of increased Treg and Th17 with pathogenesis of moyamoya disease

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.

Figure 1

The percentage of peripheral Treg and Th17 cells in MMD patients, atherothrombotic stroke patients and controls. Both the levels of Treg and Th17 were significantly increased in MMD patients compared to other groups. (A,B) Representative FACS plots for Treg and Th17 cells in peripheral blood. (C) The ratio of Treg/Th17 among the three groups. (D) Each bar represents the median and quartiles of three independent experiments. *P < 0.05, **P < 0.01 and ***P < 0.001.

Figure 2

The proliferation of CD4⁺CD25⁻ T cells co-cultured with Treg (A). The suppressive function of Treg isolated from MMD patients was lower than controls. The changes of Treg subtypes in MMD patients and healthy controls. Both the percentage of FrIII Treg cells among CD4⁺CD25⁺ T cells (B) and total Treg cells (C) were significantly elevated in MMD patients. FACS plots for subtypes of Treg cells in MMD patients and healthy controls (D). Each bar represents the mean ± SD of three independent experiments. *P < 0.05 and **P < 0.01 vs. normal Treg cells group, ^## P < 0.01 vs. control group.