Ifi27l2a, also known as interferon alpha-inducible protein 27 like 2A, is an interferon-stimulated gene. It is induced by interferons for viral host defense and has been associated with pro-inflammatory cellular mechanisms [1,2,3,4,5]. It may be involved in multiple biological processes, with its role in neurodegeneration being of particular interest recently. Genetic models, such as gene knockout mice, have been crucial in exploring its functions.

In the context of aging and stroke, single-cell RNA sequencing showed Ifi27l2a was significantly up-regulated in microglia of aged mouse brains post-stroke [1,2]. Induction of Ifi27l2a in microglia can stimulate mitochondrial ROS production and promote a pro-inflammatory phenotype [1,2]. Hemizygous deletion of Ifi27l2a (Ifi27l2a+/- mice) reduced gliosis, acute and chronic brain injury, and motor function deficits in an ischemic stroke model, indicating it is a critical neuroinflammatory mediator in ischemic stroke [1,2]. In viral infection studies, Ifi27l2a -/- mice were more vulnerable to lethal West Nile virus (WNV) infection, with higher viral burden in the CNS, especially in the brain stem, cerebellum, and spinal cord. This suggests Ifi27l2a has an antiviral phenotype in subsets of cells [3]. However, deletion of Ifi27l2a in mice did not increase susceptibility to influenza A infection [4].

In conclusion, Ifi27l2a plays important roles in neuroinflammation, especially in the context of aging and stroke, as well as in antiviral defense in a cell-type-and region-specific manner. The use of Ifi27l2a KO mouse models has been instrumental in revealing its functions in these disease-related processes, providing potential therapeutic targets for ischemic stroke and insights into the body's antiviral mechanisms [1,2,3].