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

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

SUBMITTER: Butcher MJ

PROVIDER: S-EPMC3337709 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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

Butcher Matthew J MJ Gjurich Breanne N BN Phillips Tracy T Galkina Elena V EV

Circulation research 20120202 5

<h4>Rationale</h4>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.<h4>Objective</h4>To investigate the role of the IL-17A/IL-17RA axis in atherosclerosis.<h4>Methods and results</h4>We bred apolipoprotein-E-deficient (Apoe(-/-)) mice with IL-17A-deficient and IL-17 receptor A-defici ...[more]

PMID: 22302786

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Dataset Information

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

Publications

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

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