Role of the Th17/Treg functional imbalance on the development of atherosclerosis in apo E knockout mice.
- Author:
Yu-lin CHEN
1
;
Ying JIAN
;
Min-jie LIU
;
Liang ZHONG
;
Fang ZHANG
;
Wei-feng YANG
;
Zhao XU
;
Guo-fan CHEN
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Apolipoproteins E; genetics; Atherosclerosis; immunology; Disease Models, Animal; Interleukin-17; immunology; Interleukin-6; immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; T-Lymphocytes, Regulatory; immunology; Th17 Cells; immunology; Transforming Growth Factor beta1; immunology
- From: Chinese Journal of Cardiology 2013;41(5):416-421
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the role of the helper T cells (Th) 17/Treg cell imbalance on the development of atherogenesis in apo E knockout mice.
METHODSApo E(-/-) mice were examined at age of 6, 12, 24 and 48 weeks (n = 10 each). Age matched C57/B6 mice served as controls. The number of Th17, Treg and dendritic cell (DC) was detected by flow cytometry. The levels of interleukin(IL)-6, IL-17A and transforming growth factor(TGF)-β1 were detected by ELISA. The suppression ability of Treg was evaluated by mixed lymphocyte reaction.
RESULTSWith increasing ages, the frequencies of Th17 and Treg in CD4(+) T cells were increased (Th17 ratio from 1.00% to 3.14%; Treg ratio from 8.08% to 27.80%) and the level of IL-17A was up-regulated [from (87 ± 15) pg/ml to (191 ± 26) pg/ml], but the rate of Th17/Treg cell and the level of TGF-β1 remained stable during atherogenesis in apo E knockout mice. Furthermore, the phenotype of splenic DC was matured and the blood level of IL-6 was up-regulated [from (43 ± 5) pg/ml to (104 ± 11) pg/ml] with aging in apo E(-/-) mice. Addition of IL-6 to T cells reversed the ability of Treg to suppress the proliferation of effective T cells.
CONCLUSIONDC overactivation, subsequent increased secretion of IL-6, inhibition of Treg cell function and the Th17/Treg cell imbalance play key roles on the atherogenesis in apo E(-/-) mice.