Hypoxia is now thought to contribute significantly to the pathogenesis of CRS via the stabilization and accumulation of intracellular hypoxia-induced factor 1a (HIF-1a) protein, which translocates to the nucleus where it can modulate the expression of target genes including TSLP. In human NECs, hypoxic conditions led to the upregulation of HIF-1a and the subsequent upregulation of TSLP, IL-25, and IL-33 mRNA and downstream T2 cytokines [60]. This evidence concerns the gene IL25 and congenital rubella syndrome.