title: Interleukin-17A deficiency accelerates unstable atherosclerotic plaque formation in apolipoprotein E-deficient mice.
abstract: OBJECTIVE
  Interleukin(IL)-17A, an inflammatory cytokine, has been implicated in atherosclerosis, in which inflammatory cells within atherosclerotic plaques express IL-17A. However, its role in the development of atheroscelrosis remains to be controversial.
  
  
  RESULTS
  To directly examine the role of IL-17A in atherosclerosis, we generated apolipoprotein E (ApoE)/IL-17A double-deficient (ApoE(-/-)IL-17A(-/-)) mice. Mice were fed with high-fat diet (HFD) for either 8 or 16 weeks, both starting at ages of 6 to 8 weeks. We found that splenic CD4(+) T-cells produced high amounts of IL-17A in ApoE(-/-) mice after HFD feeding for 8 weeks. Atherosclerosis was significantly accelerated in HFD-fed ApoE(-/-)IL-17A(-/-) mice compared with ApoE(-/-) mice. Splenic CD4(+) T-cells of ApoE(-/-)IL-17A(-/-) mice after HFD feeding for 8 weeks, but not for 16 weeks, exhibited increased interferon gamma and decreased IL-5 production. Importantly, formation of vulnerable plaque as evidenced by reduced numbers of vascular smooth muscle cells and reduced type I collagen deposition in the plaque was detected in ApoE(-/-)IL-17A(-/-) mice after HFD feeding for 8 weeks.
  
  
  CONCLUSIONS
  These results suggest that IL-17A regulates the early phase of atherosclerosis development after HFD feeding and plaque stability, at least partly if not all by modulating interferon gamma and IL-5 production from CD4(+) T-cells.
authors: Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815, Japan.
authors: Keiko
authors: K
authors: Danzaki
authors: Yutaka
authors: Y
authors: Matsui
authors: Masahiro
authors: M
authors: Ikesue
authors: Daichi
authors: D
authors: Ohta
authors: Koyu
authors: K
authors: Ito
authors: Masashi
authors: M
authors: Kanayama
authors: Daisuke
authors: D
authors: Kurotaki
authors: Junko
authors: J
authors: Morimoto
authors: Yoichiro
authors: Y
authors: Iwakura
authors: Hideo
authors: H
authors: Yagita
authors: Hiroyuki
authors: H
authors: Tsutsui
authors: Toshimitsu
authors: T
authors: Uede
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004041:Dietary Fats / Q000009:adverse effects; D004195:Disease Models, Animal; D018450:Disease Progression; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000172:deficiency* / Q000235:genetics / Q000627:therapeutic use; D015848:Interleukin-5 / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control
chemical_list: D001057:Apolipoproteins E; D004041:Dietary Fats; D007074:Immunoglobulin G; D020381:Interleukin-17; D015848:Interleukin-5; D007371:Interferon-gamma