Murine aortic vascular cells produce IL-17C and support inflammation in atherosclerosis. (CCR6P.271)

Abstract

Abstract The progression of atherosclerotic lesions involves regular communication between arterial hematopoetic cells and vascular cells through cytokine and chemokine networks. While recent evidence has demonstrated the presence of Interleukin-17A (IL-17A)-producing T cells within atherosclerotic Apolipoprotein E-deficient (Apoe-/-) aortas, the roles of the other IL-17 family members have not been explored. As several recent studies have demonstrated a pro-inflammatory role for epithelial and keratinocyte-derived IL-17C, we sought to examine aortic Il17c expression within atherosclerotic western diet-fed Apoe-/- and Il17a-/-Apoe-/- mice. Il17c mRNA was detected within the aortas of both Apoe-/- and Il17a-/-Apoe-/- mice and several major sources of aortic IL-17C were identified by flow cytometry; including smooth muscle cells (SMCs, 5±0.8%) and CD45-αSMA- cells (5.8±0.8%). Interestingly, elevated aortic IL-17C production was detected within Il17a-/-Apoe-/- mice in comparison to Apoe-/- littermates (6.16±0.24% vs 3.6±0.1%), suggesting an inverse relationship between T cell derived-IL-17A and vascular-IL-17C. To examine the effects of IL-17C and TNFα on aortic chemokine and cytokine production, we explanted whole aortas with IL-17C or IL-17C and TNFα. In this system, IL-17C broadly supported the expression of Ccl2, Ccl7, Cxcl1, Cxcl2, Cxcl5, and Il6. Together, these data suggest that SMC-derived IL-17C supports atherogenic inflammation via cytokine and chemokine production.