Interleukin-1α: Novel functions in cell senescence and antiviral response

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2022-06, Vol.154, p.155875, Article 155875
• Main Author: Frisch, Steven M.
• Format: Article
• Language: English
• Subjects: Antiviral response; Caspases - metabolism; Cell senescence; Cellular Senescence; IL-1α; Inflammation; Interleukin-1alpha - metabolism; Interleukin-1beta - metabolism; Mitophagy; NF-kB; Signal Transduction
• ISSN: 1043-4666; 1096-0023; 1096-0023
• DOI: 10.1016/j.cyto.2022.155875

•IL-1α localizes to the nucleus, cytoplasm, mitochondria and extracellular space.•This reflects a diversity of functions and processing mechanisms.•Recent results indicate a role in antiviral responses through IRF1 induction.•MTOR and Ras can induce cell senescence properties by generating mature IL-1α.•IL-1α inhibits mitophagy by binding to cardiolipin. The interleukin-1 proteins are a hub of innate inflammatory signaling that activates diverse aspects of adaptive immunity. Until recently, the IL-1α isoform was relatively incompletely understood compared with IL-1β. This review briefly summarizes novel and surprising aspects of IL-1α biology. IL-1α localizes to the nucleus, cytoplasm, mitochondria, cell membrane or extracellular space in various contexts, with corresponding distinct functions. In particular, we focus on multiple pathways by which IL-1α promotes the senescent cell phenotype, unexpectedly involving signaling molecules including mTOR, GATA4, mitochondrial cardiolipin and caspases-4/5. Finally, I review a novel pathway by which IL-1α promotes antiviral immunity.