RT info:eu-repo/semantics/article
T1 Lipin‐2 regulates the antiviral and anti‐inflammatory responses to interferon
A1 de Pablo, Nagore
A1 Meana, Clara
A1 Martínez‐García, Javier
A1 Martínez‐Vicente, Pablo
A1 Albert, Manuel
A1 Guerra, Susana
A1 Angulo, Ana
A1 Balsinde, Jesús
A1 Balboa, María A
AB 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.
SN 1469-221X
YR 2023
FD 2023
LK https://uvadoc.uva.es/handle/10324/79598
UL https://uvadoc.uva.es/handle/10324/79598
LA spa
NO EMBO Reports, Dec 2023, vol. 24, n. 12, p. e57238
DS UVaDOC
RD 05-dic-2025