This evidence points to interferon‐driven immune dysregulation as a plausible contribution to the formative and clinical cornerstones of Down syndrome, as indicated by steadily increasing interferon alpha and beta receptor subunit 1 (human) (IFNAR1) upregulation in all immune lineages tested by increased expression of the interferon receptors encoded on chromosome 21, as indicated by increased IFNAR1 surface expression in all immune lineages studied. This evidence concerns the gene IFNAR1 and Down syndrome.