Lipin-2 regulates the antiviral and anti-inflammatory responses to interferon.

Autor: de Pablo N; Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain., Meana C; Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain.; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain., Martínez-García J; Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain.; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain., Martínez-Vicente P; Immunology Unit, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain., Albert M; Departamento de Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain., Guerra S; Departamento de Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain., Angulo A; Immunology Unit, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain., Balsinde J; Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain.; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain., Balboa MA; Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, Spain.; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2023 Dec 06; Vol. 24 (12), pp. e57238. Date of Electronic Publication: 2023 Nov 06.
DOI: 10.15252/embr.202357238
Abstrakt: Interferons (IFN) are crucial antiviral and immunomodulatory cytokines that exert their function through the regulation of a myriad of genes, many of which are not yet characterized. Here, we reveal that lipin-2, a phosphatidic acid phosphatase whose mutations produce an autoinflammatory syndrome known as Majeed syndrome in humans, is regulated by IFN in a STAT-1-dependent manner. Lipin-2 inhibits viral replication both in vitro and in vivo. Moreover, lipin-2 also acts as a regulator of inflammation in a viral context by reducing the signaling through TLR3 and the generation of ROS and release of mtDNA that ultimately activate the NLRP3 inflammasome. Inhibitors of mtDNA release from mitochondria restrict IL-1β production in lipin-2-deficient animals in a model of viral infection. Finally, analyses of databases from COVID-19 patients show that LPIN2 expression levels negatively correlate with the severity of the disease. Overall, these results uncover novel regulatory mechanisms of the IFN response driven by lipin-2 and open new perspectives for the future management of patients with LPIN2 mutations.
(© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
Databáze: MEDLINE
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