Age-associated alteration in Th17 cell response is related to endothelial cell senescence and atherosclerotic cerebral infarction.

T-helper 17 (Th17) cells produce Interleukin-17 (IL-17) that plays an important role in host-defense. However, little is known whether aging affects the functions of human Th17 cells. In this study, we examine age-associated alteration in Th17-cell response; correlation between Th17-cells and endothelial cell senescence; and the occurrence of acute cerebral infarction (ACI). First, we examined Th17-frequency, phenotyping, key transcription factors, and relevant cytokines in healthy elderly, middle-aged and young-people along with elderly-patients with ACI. We detected levels of endothelial cell senescence markers in mRNA and inflammatory biomarker in serum among the groups. Correlations of Th17 frequency to levels of cytokines and endothelial cell senescence biomarkers have been analyzed. Finally, effects of IL-17 on endothelial cell senescence were explored in vitro. Our study demonstrated that healthy elderly-people have an increased Th17 frequency, RORγt expression and Th17 related cytokines (IL-17, IL-6) levels in peripheral blood compared to healthy middle-aged and young-people. Furthermore, elderly-ACI patients also have an increased Th17 expression as compared to healthy elderly-people. There was no significant difference in levels of memory Th17 frequency among the 4 groups, indicating that IL-17 is mainly produced by memory CD4+ T cells. There were no significant correlations between Th17 frequencies, levels of cytokines, inflammatory biomarkers in serum and endothelial cell senescence biomarkers in mRNA. Cell experiments about human umbilical vein endothelial cells (HUVECs) co-culture with IL-17 demonstrated that IL-17 promotes endothelial cell senescence which is closely related to ACI occurrence. Our results suggested that aging and ACI occurrence strengthen Th17-cell response. Th17/IL-17 may promote endothelial cell senescence, subsequently contributing to ACI occurrence in humans.