The IL-17A/IL-17RA axis plays a proatherogenic role via the regulation of aortic myeloid cell recruitment

Circ Res. 2012 Mar 2;110(5):675-87. doi: 10.1161/CIRCRESAHA.111.261784. Epub 2012 Feb 2.


Rationale: Atherosclerosis is a disease of large- and medium-sized arteries that is characterized by chronic vascular inflammation. While the role of Th1, Th2, and T-regulatory subsets in atherogenesis is established, the involvement of IL-17A-producing cells remains unclear.

Objective: To investigate the role of the IL-17A/IL-17RA axis in atherosclerosis.

Methods and results: We bred apolipoprotein-E-deficient (Apoe(-/-)) mice with IL-17A-deficient and IL-17 receptor A-deficient mice to generate Il17a(-/-)Apoe(-/-) and Il17ra(-/-)Apoe(-/-) mice. Western diet fed Il17a(-/-)Apoe(-/-) and Il17ra(-/-)Apoe(-/-) mice had smaller atherosclerotic plaques in the aortic arch and aortic roots, but showed little difference in plaque burden in the thoracoabdominal aorta in comparison with Apoe(-/-) controls. Flow cytometric analysis of Il17a(-/-)Apoe(-/-) and Il17ra(-/-)Apoe(-/-) aortas revealed that deficiency of IL-17A/IL-17RA preferentially reduced aortic arch, but not thoracoabdominal aortic T cell, neutrophil, and macrophage content in comparison with Apoe(-/-) aortic segments. In contrast to ubiquitous IL-17RA expression throughout the aorta, IL-17A was preferentially expressed within the aortic arch of WD-fed Apoe(-/-) mice. Deficiency of IL-17A or IL-17RA reduced aortic arch, but not thoracoabdominal aortic TNFα and CXCL2 expression. Aortic vascular IL-17RA supports monocyte adherence to explanted aortas in ex vivo adhesion assays. Short-term homing experiments revealed that the recruitment of adoptively transferred monocytes and neutrophils to the aortas of Il17ra(-/-)Apoe(-/-) mice is impaired in comparison with Apoe(-/-) recipients.

Conclusions: The IL-17A/IL-17RA axis increases aortic arch inflammation during atherogenesis through the induction of aortic chemokines, and the acceleration of neutrophil and monocyte recruitment to this site.

Publication types

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

MeSH terms

  • Animals
  • Aorta, Abdominal / metabolism
  • Aorta, Abdominal / pathology*
  • Aorta, Abdominal / physiopathology*
  • Aorta, Thoracic / metabolism
  • Aorta, Thoracic / pathology
  • Aorta, Thoracic / physiopathology
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Apolipoproteins E / physiology
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology*
  • Atherosclerosis / physiopathology*
  • Cell Movement / physiology
  • Chemokine CXCL2 / metabolism
  • Disease Models, Animal
  • Interleukin-17 / deficiency
  • Interleukin-17 / genetics
  • Interleukin-17 / physiology*
  • Mice
  • Mice, Knockout
  • Monocytes / pathology
  • Myeloid Cells / pathology*
  • Neutrophils / pathology
  • Plaque, Atherosclerotic / metabolism
  • Plaque, Atherosclerotic / pathology
  • Plaque, Atherosclerotic / physiopathology
  • Receptors, Interleukin-17 / deficiency
  • Receptors, Interleukin-17 / genetics
  • Receptors, Interleukin-17 / physiology*
  • Tumor Necrosis Factor-alpha / metabolism


  • Apolipoproteins E
  • Chemokine CXCL2
  • Cxcl2 protein, mouse
  • Il17ra protein, mouse
  • Interleukin-17
  • Receptors, Interleukin-17
  • Tumor Necrosis Factor-alpha