134858 20260217205451.0 doi 10.1038/s41418-024-01278-6 sideral 138374 ART-2024-138374 eng Albert, Marie-Christine Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality 2024 Access copy available to the general public Unrestricted The dysregulated immune response and inflammation resulting in severe COVID-19 are still incompletely understood. Having recently determined that aberrant death-ligand-induced cell death can cause lethal inflammation, we hypothesized that this process might also cause or contribute to inflammatory disease and lung failure following SARS-CoV-2 infection. To test this hypothesis, we developed a novel mouse-adapted SARS-CoV-2 model (MA20) that recapitulates key pathological features of COVID-19. Concomitantly with occurrence of cell death and inflammation, FasL expression was significantly increased on inflammatory monocytic macrophages and NK cells in the lungs of MA20-infected mice. Importantly, therapeutic FasL inhibition markedly increased survival of both, young and old MA20-infected mice coincident with substantially reduced cell death and inflammation in their lungs. Intriguingly, FasL was also increased in the bronchoalveolar lavage fluid of critically-ill COVID-19 patients. Together, these results identify FasL as a crucial host factor driving the immuno-pathology that underlies COVID-19 severity and lethality, and imply that patients with severe COVID-19 may significantly benefit from therapeutic inhibition of FasL. info:eu-repo/grantAgreement/ES/AEI/PID2019-104090RB-I00 info:eu-repo/grantAgreement/ES/AEI/PID2020-113963RB-I00 info:eu-repo/grantAgreement/ES/DGA/B29-20R info:eu-repo/grantAgreement/ES/DGA/E34-17R info:eu-repo/grantAgreement/ES/DGA/LMP58-18 info:eu-repo/grantAgreement/ES/ISCIII/CB21-13-00087 info:eu-repo/grantAgreement/ES/ISCIII/COV20-00308 info:eu-repo/grantAgreement/ES/MICINN AEI/PID2022-136362NB-I00 info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es 15.4 2024 CELL BIOLOGY 13 / 204 = 0.064 2024 Q1 T1 BIOCHEMISTRY & MOLECULAR BIOLOGY 8 / 320 = 0.025 2024 Q1 T1 4.866 2024 Molecular Biology 2024 Q1 Cell Biology 2024 Q1 29.0 2024 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Uranga-Murillo, Iratxe Arias, Maykel (orcid)0000-0002-9730-2210 De Miguel, Diego (orcid)0000-0002-8486-8514 Peña, Natacha Montinaro, Antonella Varanda, Ana Beatriz Theobald, Sebastian J. Areso, Itziar Saggau, Julia Koch, Manuel Liccardi, Gianmaria Peltzer, Nieves Rybniker, Jan Hurtado-Guerrero, Ramón (orcid)0000-0002-3122-9401 Merino, Pedro Universidad de Zaragoza (orcid)0000-0002-2202-3460 Monzón, Marta Universidad de Zaragoza (orcid)0000-0002-2787-9671 Badiola, Juan J. Universidad de Zaragoza (orcid)0000-0002-7173-7216 Reindl-Schwaighofer, Roman Sanz-Pamplona, Rebeca Cebollada-Solanas, Alberto (orcid)0000-0002-3312-7759 Megyesfalvi, Zsolt Dome, Balazs Secrier, Maria Hartmann, Boris Bergmann, Michael Pardo, Julián Universidad de Zaragoza (orcid)0000-0003-0154-0730 Walczak, Henning 1003 443 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Histología 1009 773 Universidad de Zaragoza Dpto. Patología Animal Área Sanidad Animal 1011 566 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Inmunología 2013 765 Universidad de Zaragoza Dpto. Química Orgánica Área Química Orgánica 31 (2024), 544–557 Cell death differ. Cell Death and Differentiation 1350-9047 6949291 http://zaguan.unizar.es/record/134858/files/texto_completo.pdf Versión publicada 3059880 http://zaguan.unizar.es/record/134858/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:134858 articulos driver 2026-02-17-20:19:02 ARTICLE