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

Emily Smith, Konkal Matt R. Prasad, Matthew Butcher, Anca Dobrian, Jay K. Kolls, Klaus Ley, Elena Galkina

Research output: Contribution to journalArticlepeer-review

346 Scopus citations

Abstract

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 γδ 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.

Original languageEnglish (US)
Pages (from-to)1746-1755
Number of pages10
JournalCirculation
Volume121
Issue number15
DOIs
StatePublished - Apr 2010
Externally publishedYes

Keywords

  • Aorta
  • Atherosclerosis
  • Immune system
  • Inflammation
  • Interleukin-17
  • Lymphocytes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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