Academic Journal
Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality
| العنوان: | Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality |
|---|---|
| المؤلفون: | Albert, MC, Uranga-Murillo, I, Arias, M, De Miguel, D, Peña, N, Montinaro, A, Varanda, AB, Theobald, SJ, Areso, I, Saggau, J, Koch, M, Liccardi, G, Peltzer, N, Rybniker, J, Hurtado-Guerrero, R, Merino, P, Monzón, M, Badiola, JJ, Reindl-Schwaighofer, R, Sanz-Pamplona, R, Cebollada-Solanas, A, Megyesfalvi, Z, Dome, B, Secrier, M, Hartmann, B, Bergmann, M, Pardo, J, Walczak, H |
| المصدر: | Cell Death & Differentiation (2024) (In press). |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2024 |
| المجموعة: | University College London: UCL Discovery |
| مصطلحات موضوعية: | Acute inflammation, Cell death and immune response, Immunopathogenesis |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| Relation: | https://discovery.ucl.ac.uk/id/eprint/10189936/1/s41418-024-01278-6.pdf; https://discovery.ucl.ac.uk/id/eprint/10189936/ |
| الاتاحة: | https://discovery.ucl.ac.uk/id/eprint/10189936/1/s41418-024-01278-6.pdf https://discovery.ucl.ac.uk/id/eprint/10189936/ |
| Rights: | open |
| رقم الانضمام: | edsbas.1566AD3C |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |