SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids
Chiu Wang ChauiD, Alex ToiD, Rex K.H. Au-YeungiD, Kaiming TangiD, Yang XiangiD, Degong Ruan, Lanlan ZhangiD, Hera Wong, Shihui ZhangiD, Man Ting AuiD, Seok Hwan ChungiD, Euijeong SongiD, Dong‐Hee ChoiiD, Pentao LiuiD, Shuofeng YuaniD, Chunyi WeniD, Ryohichi SugimuraiD
Abstract
SARS-CoV-2 provokes devastating tissue damage by cytokine release syndrome and leads to multi-organ failure. Modeling the process of immune cell activation and subsequent tissue damage is a significant task. Organoids from human tissues advanced our understanding of SARS-CoV-2 infection mechanisms though, they are missing crucial components: immune cells and endothelial cells. This study aims to generate organoids with these components. We established vascular immune organoids from human pluripotent stem cells and examined the effect of SARS-CoV-2 infection. We demonstrated that infections activated inflammatory macrophages. Notably, the upregulation of interferon signaling supports macrophages role in cytokine release syndrome. We propose vascular immune organoids are a useful platform to model and discover factors that ameliorate SARS-CoV-2-mediated cytokine release syndrome.
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