GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE320nnn/GSE320348/suppl/GSE320348_ATAC_joint_peaks.saf.counts.tsv.gzftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE320nnn/GSE320348/suppl/filelist.txtftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE320nnn/GSE320348/suppl/GSE320348_RAW.tarftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE320nnn/GSE320348/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE320348GEOGSEfalseA cell-intrinsic glucocorticoid biosynthesis and sensing circuit maintains homeostatic Th17 cell state [ATAC-seq]T helper 17 (Th17) cells are heterogeneous; homeostatic Th17 (Th17Hom) cells maintain tissue homeostasis and pro-inflammatory Th17 (Th17Inf) cells drive autoimmune inflammation. IL-23 drives Th17Inf, but the signals that maintain Th17Hom remain unclear. Here, we found that differential glucocorticoid (GC) production downstream of CYP11A1, a critical enzyme for steroidogenesis, distinguished Th17Hom cells from Th17Inf cells. Although TCR signaling opened the Cyp11a1 locus, TGFβ1 and IL-6, key cytokines for Th17Hom cell differentiation, maintained and amplified Cyp11a1. Th17Hom cell-derived GC signaled through the glucocorticoid receptor (GR), which was higher in Th17Hom cells compared to Th17Inf cells, thereby forming a circuit that maintained the homeostatic state. Integration of multi-omics data from CYP11A1- and GR-deficient Th17Hom cells revealed a gene network underlying this circuit. TGFβ1, a key node in the network, restored GC sensing to Th17Inf. We thus identify a GC signaling circuit that maintains Th17 homeostasis with implications for treating Th17-mediated autoimmunity.2026/06/12GSE320348GSM9541280GSM9541281GSM9541282GSM9541283GSM9541284GSM9541285GSM9541286GSM9541287GSM9541288GSM9541289GSM9541279GSM954129032159320348Mus musculus