GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296187/suppl/GSE296187_gene_expression_matrix.csv.gzftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296187/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296187GEOGSEfalseInterleukin-23 promotes a pro-inflammatory Th17 cell state by stabilizing RORγt and suppressing glucocorticoid receptor activity IInterleukin-23 receptor (IL-23R) signaling is critical for the generation of pro-inflammatory CD4+ IL-17-producing T cells (Th17) that can drive autoimmune tissue inflammation, but the underlying mechanisms are not clear. We integrated phosphoproteomic and transcriptomic data downstream of IL-23R and IL-12R, which share a common subunit, to identify mechanisms engaged specifically by IL-23. We identified chromodomain helicase DNA-binding protein 1 (CHD1), an epigenetic regulator, and the glucocorticoid receptor (GR), a transcription factor (TF), as mediators of IL-23R signaling. IL-23R activation promoted CHD1 interaction with TF STAT3 and co-binding at the TF RORγt locus to enforce a pro-inflammatory Th17 state. Conversely, IL-23R signaling altered phosphorylation of the GR, thereby preventing its activation and nuclear translocation, ultimately impairing GR-driven inhibition of pro-inflammatory Th17 gene programs. Our findings uncover two mechanisms by which IL-23 promotes a pro-inflammatory Th17 cell state, offering potential therapeutic targets for treating Th17-driven autoimmune tissue inflammation and restoring homeostasis.2026/06/12GSE296187GSM8966619GSM8966637GSM8966615GSM8966638GSM8966616GSM8966639GSM8966617GSM8966618GSM8966633GSM8966634GSM8966635GSM8966636GSM8966630GSM8966631GSM8966632GSM8966626GSM8966627GSM8966628GSM8966629GSM8966622GSM8966623GSM8966624GSM8966625GSM8966640GSM8966641GSM8966642GSM8966620GSM896662116791296187Homo sapiens