Immunomodulatory effects of T helper 17 cells and regulatory T cells on cerebral ischemia

Abstract

The aim of the present study was to analyze the relationship between cerebral ischemia and immune effects. A total of 70 Kunming mice were randomly divided into two groups: a model group (60 mice) and a sham group (10 mice). The model group was divided into six subgroups (10 mice per group) which were categorized according to the following time periods of treatment: 6 h, 12 h, 24 h, 48 h, 72 h and 5 days. The temporary middle cerebral artery occlusion (tMCAO) mouse model was established using intracavitary suture. The degree of brain injury was evaluated by detecting the neurological deficit score (NDS). Following cerebral ischemia reperfusion, the edema of the brain tissue was aggravated, and the infarction area was increased. At 48 h, the volume of the cerebral infarction reached a peak (44.4±3.2%) and then it decreased. The NDS score gradually decreased, and the nerve function was gradually restored. At 6 h, the NDS score was 4.6±0.55, whereas at the 5 d time point, it was significantly decreased (P less than 0.05) to 2.2±0.45. Flow cytometry analysis indicated that the percentage of Th17 cells increased gradually following ischemia. At 24 h, the percentage of Th17 cells reached its maximum value (0.70±0.10%) compared with the sham and the 5 d groups (P less than 0.05). At 24 h, the percentage of Th17 cells reached the lowest value (0.9±0.29%), whereas at the 5 d time point it increased significantly (3.2±0.49%) compared with the normal level (P less than 0.05). The secretion of Th17 and Treg-associated cytokines was consistent with the number of Th17 and Treg cells following ischemia. However, the levels of IL-17A in the brain tissues and the serum indicated a tendency to increase following the prolongation of ischemia. This marker reached the maximum levels on day 5. The IL-17 brain level was 77.9±5.11pg/ml, whereas the serum level was 29.44±3.06pg/ml. The changes in the secretion of the Th17 and Treg-related inflammatory cytokines were consistent with the changes in the cell ratio of Th17 and Treg cells. A significant correlation was noted between the two groups and the degree of ischemic brain injury. The results suggested that the functional status of Th17/Treg cells was imbalanced following cerebral ischemia