Blockade of interleukin-17A results in reduced atherosclerosis in apolipoprotein E-deficient mice

Circulation. 2010 Apr 20;121(15):1746-55. doi: 10.1161/CIRCULATIONAHA.109.924886. Epub 2010 Apr 5.


Background: T cells play an important role during the immune response that accompanies atherosclerosis. To date, the role for interleukin (IL)-17A in atherogenesis is not well defined. Here, we tested the hypothesis that atherosclerosis-prone conditions induce the differentiation of IL-17A-producing T cells, which in turn promote atherosclerosis.

Methods and results: IL-17A was found to be elevated in the plasma and tissues of apolipoprotein E-deficient (Apoe(-/-)) mice. IL-17A-expressing T cells were significantly increased in the aortas, spleen, and lamina propria of aged Apoe(-/-) mice compared with age-matched C57BL/6 mice. IL-17A(+) T cells resided in both adventitia and aortas of aged Apoe(-/-) mice fed a chow diet. Elevated levels of IL-17A(+) T cells were also detected in the aortas of 21-week-old Apoe(-/-) mice fed a Western diet for 15 weeks. IL-17A(+) T cells were characterized as predominantly CD4(+) T helper 17 (Th17) cells and gammadelta(+) T cells. Blockade of IL-17A in Apoe(-/-) mice by use of adenovirus-produced IL-17 receptor A reduced plaque burden in Apoe(-/-) mice fed a Western diet for 15 weeks. In addition, the treatment diminished circulating IL-6 and granulocyte colony-stimulating factor levels and limited CXCL1 expression and macrophage content within the aortas. Conversely, IL-17A treatment of whole aorta isolated from Apoe(-/-) mice promoted aortic CXCL1 expression and monocyte adhesion in an ex vivo adhesion assay.

Conclusions: These results demonstrate that atherosclerosis-prone conditions induce the differentiation of IL-17A-producing T cells. IL-17A plays a proatherogenic inflammatory role during atherogenesis by promoting monocyte/macrophage recruitment into the aortic wall.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / cytology
  • Aorta / immunology
  • Apolipoproteins E / genetics*
  • Atherosclerosis / genetics
  • Atherosclerosis / immunology*
  • Atherosclerosis / metabolism
  • Cell Differentiation / immunology
  • Chemokine CXCL1 / metabolism
  • Disease Progression
  • Female
  • Granulocyte Colony-Stimulating Factor / blood
  • Interleukin-17 / antagonists & inhibitors
  • Interleukin-17 / blood*
  • Interleukin-6 / blood
  • Macrophages / cytology
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Monocytes / cytology
  • Monocytes / immunology
  • Mucous Membrane / cytology
  • Mucous Membrane / immunology
  • Recombinant Fusion Proteins / pharmacology
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocytes / immunology*


  • Apolipoproteins E
  • Chemokine CXCL1
  • Cxcl1 protein, mouse
  • Interleukin-17
  • Interleukin-6
  • Recombinant Fusion Proteins
  • Granulocyte Colony-Stimulating Factor