Abstract 186: Aortic IL-17C Producing Cells in Atherosclerosis.

Abstract

The progression of atherosclerosis from fatty acid streaks to complex lesions involves regular communication between hematopoetic cells within the arterial wall and vascular cells via cytokine and chemokine networks. Recent evidence has demonstrated the presence of Interleukin-17A (IL-17A)-producing T cells within atherosclerotic Apolipoprotein E-deficient (Apoe-/-) aortas. IL-17A is a member of the IL-17 cytokine family, which consists of six related isoforms (IL-17A-IL-17F). While the functions of IL-17A, IL-17E, and IL-17F are the subject of ongoing studies, the roles and producers of IL-17B and IL-17C remain elusive. Recent studies have demonstrated a pro-inflammatory role for epithelial cell and keratinocyte-derived IL-17C in the context of experimental colitis, and psoriasis. In the present study, we sought to examine the expression of IL-17C within the aortas of atherosclerotic Apoe-/- and Il17a-/-Apoe-/- mice. We detected Il17c mRNA within the aortas of both 12-week western diet-fed Apoe-/- and Il17a-/-Apoe-/- mice. To further identify and characterize the cellular sources of aortic IL-17C, we examined aortic leukocytes and vascular cells by flow cytometry. We identified several major cellular producers of IL-17C in vivo, including a major population of smooth muscle cells (5±0.8% of Apoe-/- CD45-αSMA+ SMCs) and a population of CD45-αSMA- cells (5.8±0.8% of Apoe-/- CD45-αSMA- cells). Interestingly, the percentage of aortic IL-17C producing cells was elevated within 12 week western diet-fed Il17a-/-Apoe-/- mice in comparison to Apoe-/- littermates (6.16±0.24% of the Il17a-/-Apoe-/- aorta vs 3.6±0.1% of the Apoe-/- aorta), suggesting an inverse relationship between T cell derived-IL-17A and vascular-IL-17C. To examine the effects of IL-17C and the possibility of synergy between TNFα and IL-17C on aortic chemokine and cytokine production, we explanted and treated whole aortas with IL-17C or IL-17C and TNFα in vitro. IL-17C with and without TNFα broadly supported the expression of Ccl2, Ccl7, Cxcl1, Cxcl2, Cxcl5, and Il6 in explanted WD Apoe-/- aortas. Together, these results suggest that vascular smooth muscle cell-derived IL-17C may play a pro-inflammatory role in atherosclerosis via the production of chemokines and cytokines.