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Peshkova IO , Aghayev T , Fatkhullina AR , Makhov P , Titerina EK , Eguchi S , Tan YF , Kossenkov AV , Khoreva MV , Gankovskaya LV , Sykes SM , Koltsova EK
IL-27 receptor-regulated stress myelopoiesis drives abdominal aortic aneurysm development
Nat Commun. 2019 Nov 6;10(1) :5046
PMID: 31695038 PMCID: PMC6834661
AbstractAbdominal aortic aneurysm (AAA) is a prevalent life-threatening disease, where aortic wall degradation is mediated by accumulated immune cells. Although 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. Mitigation of AAA is associated with a blunted accumulation of myeloid cells in the aorta due to the attenuation of Angiotensin II (Ang II)-induced HSC expansion. IL-27R signaling is required to induce transcriptional programming to overcome HSC quiescence and increase differentiation and output of mature myeloid cells in response to stress stimuli to promote their accumulation in the diseased aorta. Overall, our studies illuminate how a prominent vascular disease can be distantly driven by a cytokine-dependent regulation of bone marrow precursors.
Notes2041-1723 Peshkova, Iuliia O Aghayev, Turan Fatkhullina, Aliia R Makhov, Petr Titerina, Elizaveta K Eguchi, Satoru Tan, Yin Fei Kossenkov, Andrew V Khoreva, Marina V ORCID: http://orcid.org/0000-0002-6224-2510 Gankovskaya, Lyudmila V Sykes, Stephen M Koltsova, Ekaterina K RSG-18-195-01-DDC/American Cancer Society (American Cancer Society, Inc.) W81XWH-18-1-0472/U.S. Department of Defense (United States Department of Defense) Journal Article England Nat Commun. 2019 Nov 6;10(1):5046. doi: 10.1038/s41467-019-13017-4.