Abstract 552: IL-17C-Producing Aortic Smooth Muscle Cells Play a Pro-Atherogenic Role Via the Recruitment of Inflammatory IL-17A+ T Cells
Atherosclerosis is characterized by frequent communication between infiltrating leukocytes and vascular cells, through chemokine and cytokine networks. Various IL-17 cytokine family members are detected within atherosclerotic plaques; however the involvement of IL-17B-IL-17E has not been thoroughly examined. Aortic IL-17 cytokines were initially profiled and Il17a, Il17f, and Il17c mRNA expression was found to be elevated in Apoe-/- aortas in comparison to C57Bl6 controls. To determine the cellular sources of aortic IL-17C, aortic IL-17C-producing cells were phenotyped by flow cytometry. Surprisingly, these experiments revealed a major population of IL-17C-producing smooth muscle cells within Apoe-/- versus C57Bl6 aortas. To determine the role of IL-17C in atherosclerosis, we generated Il17c-/-Apoe-/- mice and compared 12 week western diet-fed Apoe-/- and Il17c-/-Apoe-/- mice. Atherosclerotic lesions were reduced by 42±2.6% in WD-fed Il17c-/-Apoe-/- aortas in comparison to Apoe-/- controls. Flow cytometric analyses of Il17c-/-Apoe-/- mice revealed a reduction in the number of aortic leukocytes, macrophages, neutrophils, and T cells, which corresponded with smaller atherosclerotic lesions (40±5%). However, the percentage and number of aortic IL-17A+ TCRγδ T cells and Th17 cells were disproportionately reduced within Il17c-/-Apoe-/- aortas (70±5%). We hypothesized that IL-17C might support the recruitment of Th17 cells to the aorta. To study comparative Th17 migration, Apoe-/- T cells were transferred to western diet-fed Il17c-/-Apoe-/- and Apoe-/- recipients and examined for Th1 and Th17 migration 48 hours post transfer. We found diminished accumulation of Th17, but not Th1 T cells, in the aortas of Il17c-/-Apoe-/- versus Apoe-/- recipients. Thus smooth muscle cell-derived IL-17C plays a pro-atherogenic role by supporting the recruitment of Th17 cells to atherosclerotic lesions.
Author Disclosures: M.J. Butcher: None. E.V. Galkina: None.
This research has received full or partial funding support from the American Heart Association.
- © 2015 by American Heart Association, Inc.