Innate immune cell activation causes lung fibrosis in a humanized model of long COVID.

Autor:	Cui L; Department of Pathology, Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305., Fang Z; Department of Anesthesiology, Pain and Perioperative Medicine, Stanford University School of Medicine, Stanford, CA 94305., De Souza CM; Department of Pathology, Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305., Lerbs T; Department of Pathology, Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305., Guan Y; Department of Anesthesiology, Pain and Perioperative Medicine, Stanford University School of Medicine, Stanford, CA 94305., Li I; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA 94305.; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305., Charu V; Department of Pathology, Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305., Chen SY; Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan., Weissman I; Department of Pathology, Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.; Ludwig Center at Stanford University, Stanford, CA 94305., Wernig G; Department of Pathology, Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2023 Mar 07; Vol. 120 (10), pp. e2217199120. Date of Electronic Publication: 2023 Feb 27.
DOI:	10.1073/pnas.2217199120
Abstrakt:	COVID-19 remains a global pandemic of an unprecedented magnitude with millions of people now developing "COVID lung fibrosis." Single-cell transcriptomics of lungs of patients with long COVID revealed a unique immune signature demonstrating the upregulation of key proinflammatory and innate immune effector genes CD47, IL-6, and JUN. We modeled the transition to lung fibrosis after COVID and profiled the immune response with single-cell mass cytometry in JUN mice. These studies revealed that COVID mediated chronic immune activation reminiscent to long COVID in humans. It was characterized by increased CD47, IL-6, and phospho-JUN (pJUN) expression which correlated with disease severity and pathogenic fibroblast populations. When we subsequently treated a humanized COVID lung fibrosis model by combined blockade of inflammation and fibrosis, we not only ameliorated fibrosis but also restored innate immune equilibrium indicating possible implications for clinical management of COVID lung fibrosis in patients.
Databáze:	MEDLINE
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