Figure 3.
Panel A shows the location of IFN receptors on chromosome 21, including IFNAR1, IFNAR2, IFNGR2, and IL10RB. Panel B illustrates the types of interferons (Type 1, Type 2, and Type 3) and their respective receptors (IFNAR1, IFNAR2, IFNGR2, and IL10RB) interacting with JAK1 and TYK2 proteins, leading to the transcription of IFN stimulated genes (ISGs) through STATs and IRFs. Panel C depicts a flowchart starting with IFNR triplication, leading to elevated IFN response and increased JAK/STAT signaling, followed by overexpression of ISGs, chronic immune activation and inflammation, and ultimately the clinical and developmental hallmarks of Down syndrome. Alternative sources of IFN hyperactivity, such as aneuploidy and mitochondrial dysfunction, are also mentioned.
The interferonopathy of DS. (A) Panel shows the location of IFN receptors on chromosome 21. (B) Panel illustrates the types of interferons and their respective receptors interacting with JAK1 and TYK2 proteins. (C) Panel depicts pathophysiology causing the interferonopathy in Down syndrome.