Phospholipase A2 inhibitor and LY6/PLAUR domain-containing protein PINLYP regulates type I interferon innate immunity

Autor: Zhongshun Liu, Congwei Jiang, Zhangmengxue Lei, Sihan Dong, Linlin Kuang, Chenxu Huang, Ying Gao, Mu Liu, Hui Xiao, Patrick Legembre, Jae U. Jung, Huaping Liang, Xiaozhen Liang
Rok vydání: 2021
Předmět:
Zdroj: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Popis: Significance Interferon (IFN)-mediated antiviral responses serve as the first line of the host innate immune defense against viral infection. Here we identify a previously uncharacterized protein designated phospholipase A2 inhibitor and LY6/PLAUR domain-containing protein (PINLYP), which is essential for embryonic development and plays an important role in type I IFN against pathogen infection. PINLYP deficiency impairs type I IFN production and dampens in vivo host defense against DNA and RNA virus infection. We unravel a unique actor in the type I IFN innate immunity and a potential target for the antiviral therapies.
Type I interferons (IFNs) are the first frontline of the host innate immune response against invading pathogens. Herein, we characterized an unknown protein encoded by phospholipase A2 inhibitor and LY6/PLAUR domain-containing (PINLYP) gene that interacted with TBK1 and induced type I IFN in a TBK1- and IRF3-dependent manner. Loss of PINLYP impaired the activation of IRF3 and production of IFN-β induced by DNA virus, RNA virus, and various Toll-like receptor ligands in multiple cell types. Because PINLYP deficiency in mice engendered an early embryonic lethality in mice, we generated a conditional mouse in which PINLYP was depleted in dendritic cells. Mice lacking PINLYP in dendritic cells were defective in type I IFN induction and more susceptible to lethal virus infection. Thus, PINLYP is a positive regulator of type I IFN innate immunity and important for effective host defense against viral infection.
Databáze: OpenAIRE
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