000134858 001__ 134858
000134858 005__ 20250923084421.0
000134858 0247_ $$2doi$$a10.1038/s41418-024-01278-6
000134858 0248_ $$2sideral$$a138374
000134858 037__ $$aART-2024-138374
000134858 041__ $$aeng
000134858 100__ $$aAlbert, Marie-Christine
000134858 245__ $$aIdentification of FasL as a crucial host factor driving COVID-19 pathology and lethality
000134858 260__ $$c2024
000134858 5060_ $$aAccess copy available to the general public$$fUnrestricted
000134858 5203_ $$aThe 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.
000134858 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/COV20-00308$$9info:eu-repo/grantAgreement/ES/ISCIII/CB21-13-00087$$9info:eu-repo/grantAgreement/ES/DGA/LMP58-18$$9info:eu-repo/grantAgreement/ES/DGA/E34-17R$$9info:eu-repo/grantAgreement/ES/DGA/B29-20R$$9info:eu-repo/grantAgreement/ES/AEI/PID2020-113963RB-I00$$9info:eu-repo/grantAgreement/ES/AEI/PID2019-104090RB-I00$$9info:eu-repo/grantAgreement/ES/MICINN AEI/PID2022-136362NB-I00
000134858 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000134858 590__ $$a15.4$$b2024
000134858 592__ $$a4.866$$b2024
000134858 591__ $$aCELL BIOLOGY$$b13 / 204 = 0.064$$c2024$$dQ1$$eT1
000134858 593__ $$aMolecular Biology$$c2024$$dQ1
000134858 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b8 / 319 = 0.025$$c2024$$dQ1$$eT1
000134858 593__ $$aCell Biology$$c2024$$dQ1
000134858 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000134858 700__ $$aUranga-Murillo, Iratxe
000134858 700__ $$0(orcid)0000-0002-9730-2210$$aArias, Maykel
000134858 700__ $$0(orcid)0000-0002-8486-8514$$aDe Miguel, Diego
000134858 700__ $$aPeña, Natacha
000134858 700__ $$aMontinaro, Antonella
000134858 700__ $$aVaranda, Ana Beatriz
000134858 700__ $$aTheobald, Sebastian J.
000134858 700__ $$aAreso, Itziar
000134858 700__ $$aSaggau, Julia
000134858 700__ $$aKoch, Manuel
000134858 700__ $$aLiccardi, Gianmaria
000134858 700__ $$aPeltzer, Nieves
000134858 700__ $$aRybniker, Jan
000134858 700__ $$0(orcid)0000-0002-3122-9401$$aHurtado-Guerrero, Ramón
000134858 700__ $$0(orcid)0000-0002-2202-3460$$aMerino, Pedro$$uUniversidad de Zaragoza
000134858 700__ $$0(orcid)0000-0002-2787-9671$$aMonzón, Marta$$uUniversidad de Zaragoza
000134858 700__ $$0(orcid)0000-0002-7173-7216$$aBadiola, Juan J.$$uUniversidad de Zaragoza
000134858 700__ $$aReindl-Schwaighofer, Roman
000134858 700__ $$aSanz-Pamplona, Rebeca
000134858 700__ $$0(orcid)0000-0002-3312-7759$$aCebollada-Solanas, Alberto
000134858 700__ $$aMegyesfalvi, Zsolt
000134858 700__ $$aDome, Balazs
000134858 700__ $$aSecrier, Maria
000134858 700__ $$aHartmann, Boris
000134858 700__ $$aBergmann, Michael
000134858 700__ $$0(orcid)0000-0003-0154-0730$$aPardo, Julián$$uUniversidad de Zaragoza
000134858 700__ $$aWalczak, Henning
000134858 7102_ $$11003$$2443$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Histología
000134858 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal
000134858 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología
000134858 7102_ $$12013$$2765$$aUniversidad de Zaragoza$$bDpto. Química Orgánica$$cÁrea Química Orgánica
000134858 773__ $$g31 (2024), 544–557$$pCell death differ.$$tCell Death and Differentiation$$x1350-9047
000134858 8564_ $$s6949291$$uhttps://zaguan.unizar.es/record/134858/files/texto_completo.pdf$$yVersión publicada
000134858 8564_ $$s3059880$$uhttps://zaguan.unizar.es/record/134858/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000134858 909CO $$ooai:zaguan.unizar.es:134858$$particulos$$pdriver
000134858 951__ $$a2025-09-22-14:36:10
000134858 980__ $$aARTICLE