Group 2 Innate Lymphoid Cells Protect Mice from Abdominal Aortic Aneurysm Formation via IL5 and Eosinophils

• Published in: Advanced science Vol. 10; no. 7; pp. e2206958 - n/a
• Main Authors: Zhang, Yuanyuan, Liu, Tianxiao, Deng, Zhiyong, Fang, Wenqian, Zhang, Xian, Zhang, Shuya, Wang, Minjie, Luo, Songyuan, Meng, Zhaojie, Liu, Jing, Sukhova, Galina K., Li, Dazhu, McKenzie, Andrew N. J., Libby, Peter, Shi, Guo‐Ping, Guo, Junli
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.03.2023; John Wiley and Sons Inc; Wiley
• Subjects: Abdomen; abdominal aortic aneurysm; Animals; Aortic Aneurysm, Abdominal - immunology; Aortic Aneurysm, Abdominal - pathology; Aortic Aneurysm, Abdominal - prevention & control; Aortic aneurysms; Apoptosis; Body fat; Cell growth; Coronary vessels; Cytokines; eosinophil; Eosinophils - immunology; Eosinophils - pathology; Group‐2 innate lymphoid cell; IL5; Immunity, Innate - immunology; Inflammation; Interleukin-13; Interleukin-5 - immunology; Lymphocytes; Lymphocytes - immunology; Mice; Neutrophils; Spleen; Group-2 innate lymphoid cell; IL5; eosinophil; abdominal aortic aneurysm
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202206958

Development of abdominal aortic aneurysms (AAA) enhances lesion group‐2 innate lymphoid cell (ILC2) accumulation and blood IL5. ILC2 deficiency in Rorafl/flIl7rCre/+ mice or induced ILC2 depletion in Icosfl‐DTR‐fl/+Cd4Cre/+ mice expedites AAA growth, increases lesion inflammation, but leads to systemic IL5 and eosinophil (EOS) deficiency. Mechanistic studies show that ILC2 protect mice from AAA formation via IL5 and EOS. IL5 or ILC2 from wild‐type (WT) mice, but not ILC2 from Il5−/− mice induces EOS differentiation in bone‐marrow cells from Rorafl/flIl7rCre/+ mice. IL5, IL13, and EOS or ILC2 from WT mice, but not ILC2 from Il5−/− and Il13−/− mice block SMC apoptosis and promote SMC proliferation. EOS but not ILC2 from WT or Il5−/− mice block endothelial cell (EC) adhesion molecule expression, angiogenesis, dendritic cell differentiation, and Ly6Chi monocyte polarization. Reconstitution of WT EOS and ILC2 but not Il5−/− ILC2 slows AAA growth in Rorafl/flIl7rCre/+ mice by increasing systemic EOS. Besides regulating SMC pathobiology, ILC2 play an indirect role in AAA protection via the IL5 and EOS mechanism. The group‐2 innate lymphoid cells (ILC2) slow abdominal aortic aneurysm (AAA) development by producing IL5 and IL13 to block smooth muscle cell (SMC) apoptosis and promote SMC proliferation. ILC2 also produce IL5 to promote eosinophil differentiation as an indirect mechanism to affect SMC apoptosis and proliferation, and to block endothelial cell adhesion molecule expression, angiogenesis, dendritic cell differentiation, and Ly6Chi monocyte polarization.