The Th17/Treg functional imbalance during atherogenesis in ApoE(-/-) mice.
OBJECTIVE
Atherosclerosis is a chronic inflammatory disease regulated by T lymphocyte subsets. Recently, CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells and Th17 cells have been described as two distinct subsets and have the opposite effects on autoimmunity. Clinical observation has revealed that the Th17/Treg imbalance exists in patients with acute coronary syndrome. We investigated whether the Th17/Treg functional imbalance existed during atherogenesis in ApoE(-/-) mice.


RESULTS
Th17/Treg functions at different levels including cell frequencies, related cytokine secretion and key transcription factors were investigated comparatively between ApoE(-/-) mice and their age-matched C57BL/6J mice. The results demonstrated that ApoE(-/-) mice revealed significantly increased secretion of Th17 related cytokines (IL-17 and IL-6) and expression of transcription factor (RORgammat) levels and obviously decreased number in Treg cells, secretion of Treg related cytokines (TGF-beta(1)) and expression of transcription factor (Foxp3) levels as compared with age-matched C57BL/6J mice. Th17 related mediators reached their maximum expression values at the early stage (8-16weeks of age) in ApoE(-/-) mice, and then followed by continuous depression of their expression levels. Meanwhile, the expression of Treg related mediators was much lower in ApoE(-/-) mice than in their age-matched wild-type littermates.


CONCLUSIONS
Th17/Treg functional imbalance exists during atherogenesis in ApoE(-/-) mice, suggesting a potential role of Th17/Treg imbalance in the formation and progression of atherosclerosis.
Xie
Jiang-jiao
JJ
Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
Wang
Jun
J
Tang
Ting-ting
TT
Chen
Jian
J
Gao
Xing-li
XL
Yuan
Jing
J
Zhou
Zi-hua
ZH
Liao
Meng-yang
MY
Yao
Rui
R
Yu
Xian
X
Wang
Dan
D
Cheng
Yan
Y
Liao
Yu-hua
YH
Cheng
Xiang
X
D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics / Q000276:immunology*; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*
D001057:Apolipoproteins E; D016207:Cytokines; D020381:Interleukin-17