A critical function of Th17 proinflammatory cells in the development of atherosclerotic plaque in mice.
Considerable evidence supports that the CD4(+) T cell-mediated immune response contributes to the development of atherosclerotic plaque. However, the effects of Th17 cells on atherosclerosis are not thoroughly understood. In this study, we evaluated the production and function of Th17 and Th1 cells in atherosclerotic-susceptible ApoE(-/-) mice. We observed that the proportion of Th17 cells, as well as Th1, increased in atherosclerotic ApoE(-/-) mice compared with nonatherosclerotic wild-type littermates. In ApoE(-/-) mice with atherosclerosis, the expression of IL-17 and retinoic acid-related orphan receptor γt was substantially higher in the arterial wall with plaque than in the arterial wall without plaque. Increased Th17 cells were associated with the magnitude of atherosclerotic plaque in ApoE(-/-) mice. Importantly, treatment of ApoE(-/-) mice with neutralizing anti-IL-17 Ab dramatically inhibited the development of atherosclerotic plaque, whereas rIL-17 application significantly promoted the formation of atherosclerotic plaque. These data demonstrate that Th17 cells play a critical role in atherosclerotic plaque formation in mice, which may have implications in patients with atherosclerosis.
Gao
Qi
Q
Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, China.
Jiang
Yang
Y
Ma
Tian
T
Zhu
Faliang
F
Gao
Fei
F
Zhang
Pin
P
Guo
Chun
C
Wang
Qun
Q
Wang
Xiaoyan
X
Ma
Chunhong
C
Zhang
Yun
Y
Chen
Wanjun
W
Zhang
Lining
L
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism
D001057:Apolipoproteins E; D007371:Interferon-gamma; D002784:Cholesterol