Interferon regulatory factor 1 regulation of oligodendrocyte injury and inflammatory demyelination

Oligodendrocyte injury and inflammatory demyelination are key pathological abnormalities of multiple sclerosis (MS), and its animal model, i.e., the experimental autoimmune encephalomyelitis (EAE). Traditionally, they are viewed as destructive processes secondary to a dysregulated autoimmune reaction. New evidence emerged over the last decade indicating that oligodendrocytes are not merely immune targets but rather active participants in the neuroimmune network and, in fact, can regulate the events leading to inflammatory demyelination. In this review, we are discussing the role of interferon regulatory factor 1 (IRF-1) as a master transcription factor orchestrating oligodendrocyte injury and inflammatory demyelination in MS and EAE. We are also discussing the significance of IRF-1 signaling in the induction of oligodendrocyte pyroptosis, a Caspase 1-dependent pro-inflammatory cell death, as a disease-enhancing mechanism. Finally, we are drawing attention to IRF-1 as a potential therapeutic target in MS and to the importance of investigating other oligodendrocyte-dependent disease mechanisms.