GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296401/suppl/GSE296401_CHD1_2D2_EAE_CNS.csv.gzftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296401/suppl/GSE296401_GR_2D2_EAE_CNS.csv.gzftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296401/suppl/GSE296401_CHD1_2D2_EAE_dLN.csv.gzftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296401/suppl/GSE296401_IL23R_WT_KO_Ctrl_Dex.csv.gzftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296401/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296401GEOGSEfalseInterleukin-23 promotes a pro-inflammatory Th17 cell state by stabilizing RORγt and suppressing glucocorticoid receptor activity IIInterleukin-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.2026/06/12GSE296401GSM8969703GSM8969669GSM8969702GSM8969688GSM8969666GSM8969687GSM8969668GSM8969701GSM8969700GSM8969689GSM8969667GSM8969684GSM8969683GSM8969686GSM8969685GSM8969680GSM8969682GSM8969681GSM8969677GSM8969699GSM8969698GSM8969676GSM8969679GSM8969678GSM8969695GSM8969673GSM8969694GSM8969672GSM8969697GSM8969675GSM8969674GSM8969696GSM8969691GSM8969690GSM8969671GSM8969693GSM8969692GSM89696701905721626296401Mus musculus