GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326921/primaryOK200TranscriptomicsMus musculus Genome binding/occupancy profiling by high throughput sequencingExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326921GEOGSEfalseThe chromatin assembly factor CHAF1b functions as an epigenetic amplifier of RORγt to promote Th17 pathogenicity and autoimmunityTh17 cells are double-edged regulators of mucosal defense and autoimmune inflammation, yet the chromatin mechanisms distinguishing their pathogenic state remain elusive. Here, we identify CHAF1b, a core subunit of the chromatin assembly factor CAF-1 complex, as an essential epigenetic amplifier of RORgt-driven transcription in Th17 cells. CHAF1b expression is selectively induced during Th17 differentiation and elevated in inflamed tissues from mice with experimental autoimmune encephalomyelitis (EAE) and colitis. Th17-specific deletion of Chaf1b markedly reduces IL-17A/F expression, alleviates neuroinflammation and colonic pathology, and reprograms the Th17 effector transcriptome without affecting lineage commitment. Mechanistically, CHAF1b physically associates with RORgt and co-occupies enhancer regions at the Il17a–Il17f locus, promoting chromatin accessibility and enhancer activation. Multi-omics analyses reveal that CHAF1b reinforces RORgt-driven enhancer–promoter interactions and maintains a proinflammatory Th17 epigenome. In human Th17 cells, CHAF1b similarly governs IL-17 production, and its expression declines in patients with inflammatory bowel disease following effective therapy. Collectively, these findings uncover CHAF1b as a chromatin-anchored signal amplifier that couples RORgt activity to autoimmune inflammation, highlighting its potential as a therapeutic target for Th17-mediated disorders.2026/04/08GSE326921GSM9643609GSM9643607GSM9643608GSM9643616GSM9643605GSM9643606GSM9643614GSM9643615GSM9643604GSM9643612GSM9643613GSM9643610GSM964361134290326921Mus musculus