Exp Mol Med.  2015 May;47(5):e163. 10.1038/emm.2015.19.

The enhanced expression of IL-17-secreting T cells during the early progression of atherosclerosis in ApoE-deficient mice fed on a western-type diet

• Jeon US
• Choi JP
• Kim YS
• Ryu SH
• Kim YK

• KMID: 2155655
• DOI: http://doi.org/10.1038/emm.2015.19

Abstract

Atherosclerosis is a chronic progressive inflammatory disorder and the leading cause of cardiovascular mortality. Here we assessed the dynamic changes of T-cell-derived cytokines, such as inteferon (IFN)-gamma, interleukin (IL)-17 and IL-4, during the progression of atherosclerosis in apolipoprotein E-null (ApoE(-/-)) mice, to understand the role of immune responses in different stages of atherosclerosis. Male ApoE(-/-) mice were fed a high-fat, western-type diet (WD: 21% lipid, 1.5% cholesterol) after 5 weeks of age and were compared with C57BL/6 wild-type control mice fed a standard chow diet. Atherosclerotic lesions appeared in the aortic sinus of ApoE(-/-) mice 4 weeks after WD and the lesions progressed and occupied >50% of the total sinus area 16 weeks after WD. Aortic IL-17 mRNA and protein expression started to increase in ApoE(-/-) mice after 4 weeks on the WD and peaked at around 8-12 weeks on the WD. In terms of systemic expression of T-cell-derived cytokines, IL-17 production from splenocytes after anti-CD3/CD28 stimuli increased from 4 weeks on the WD, peaked at 12 weeks and returned to control levels at 16 weeks. The production of IFN-gamma and IL-4 (Th1 and Th2 cytokines, respectively) from splenocytes was delayed compared with IL-17. Taken together, the present data indicate that Th17 cell response may be involved at an early stage in the development of atherosclerosis.

MeSH Terms

Animals
Aorta/metabolism/*pathology
Apolipoproteins E/*genetics
Atherosclerosis/etiology/*genetics/immunology/*pathology
Diet, High-Fat/adverse effects
Gene Deletion
Interferon-gamma/genetics
Interleukin-17/*genetics/immunology
Male
Mice, Inbred C57BL
Mice, Knockout
T-Lymphocytes/immunology/metabolism/pathology
Up-Regulation
Apolipoproteins E
Interferon-gamma
Interleukin-17