Assessment of the impact of the IL23R R381Q variant in terms of IL-23-sensitive transcript induction

We stimulated T-cell blasts from IL23R R381Q homozygotes (n = 2), healthy controls homozygous for the ancestral allele (n = 9), homozygous individuals for TYK2 P1104A (n = 2) that selectively impairs responses to IL-23, and one patient each with autosomal recessive, complete TYK2 or IL-12Rb1 deficiency with IL-12, IL-23, IL-1b, and IL-1b plus IL-23 for 6 hours and performed RNA-sequencing. We used IL-1b as an IL-23-sensitizing agent as previously reported. We found that while T-cell blasts from IL23R R381Q homozygotes respond normally to IL-12 and IL-1b, their response to IL-23 and to IL-23 plus IL-1b is impaired Overall design: Comparative gene expression profiling analysis of RNA-seq data for T-cell blasts of individuals with the IL23R R381Q derived allele and its ancestral complementary allele at the same genomic position