GSE129881
IL-27 receptor signaling regulated stress hematopoiesis drives Abdominal Aortic Aneurysm development
Abdominal Aortic Aneurysm (AAA) is a prevalent life-threatening disease, where aortic wall degradation is mediated by accumulated immune cells. Though cytokines regulate inflammation within the aorta, their contribution to AAA via distant alterations, particularly in the control of hematopoietic stem cell (HSC) differentiation remains poorly defined. Here we report a pathogenic role for the interleukin-27 receptor (IL-27R) in AAA as genetic ablation of IL-27R protects mice from the disease development, where the mitigation of AAA is associated with a blunted accumulation of myeloid cells in the aorta due to the attenuation of Ang II-induced HSC expansion. The loss of IL-27R engages transcriptional programs that promote HSCs quiescence and suppresses differentiation decreasing mature myeloid cell production and accumulation in the aorta.  Our studies illuminate how a prominent vascular disease can be distantly driven by cytokine dependent regulation of bone marrow precursors. Overall design: RNA-seq for long-term progenitors (LT-HSC), short-term progenitors (ST-HSC) from   in Apoe-/-, Apoe-/-Il27ra+/- and Apoe-/-Il27ra-/- mice  treated with PBS or AngII