Abstract 668: The Role of IL-27 Receptor Signaling in the Development of Abdominal Aortic Aneurysm

Abstract

Abdominal aortic aneurysm (AAA) is a cardiovascular disease, which is characterized by aortic wall dilation with subsequent rupture and internal bleeding. Inflammatory reactions in the vessel wall are likely essential for AAA pathogenesis, just like they are important for the development of another vascular pathology- atherosclerosis, which can predispose to AAA formation in a context-dependent manner. While inflammatory cytokines were shown to promote atherosclerosis and AAA, little is known about contribution of anti-inflammatory cytokines with regard to their ability to control vascular inflammation. Interleukin (IL)-27 signaling is required to suppress atherosclerosis development but its function in AAA remains unknown. We utilize Angiotensin II (AngII) model to evaluate the role of IL-27R signaling in pathogenesis of AAA. AngII containing pumps were surgically implanted into Il27ra-/- x Ldlr-/-; Il27ra -/- x Apoe-/- and Il27ra+/- littermate controls and AAA progression was analyzed 4 weeks later. Surprisingly, we found attenuated AAA progression in Il27ra-/- mice compared to Il27ra+/- and wt counterparts. The latter developed large AAA with visual hemorrhage into the artery wall, while Il27ra-/- mice developed small AAA with fewer myeloid cells and T cells. Moreover, opposite to aortic arches, T cells in abdominal aortas of Il27ra-/- mice produced less inflammatory IL-17A, while IFNγ production was unchanged. Interestingly, we found enhanced production of “Th2-like” cytokines IL-4 and IL-13, by NK cells and Type 2 Innate lymphoid cells (ILC2) in Il27ra deficient mice, which correlated with the protection from AAA. Overall, we conclude that immunoregulatory cytokine IL-27 can differentially control atherosclerosis and AAA development by regulating innate and adaptive immune cell recruitment and cytokine production in the aortic wall.