GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296482/suppl/GSE296482_pTh17_in_vitro_2d_GC_TGF.csv.gzftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296482/suppl/GSE296482_Cyp11a1_KO_WT_CNS.csv.gzftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296482/suppl/GSE296482_2D2_npTh17_GR.csv.gzftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296482/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296482GEOGSEfalseA cell-intrinsic glucocorticoid biosynthesis and sensing circuit maintains homeostatic Th17 cell state [RNA-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.2026/06/12GSE296482GSM8971090GSM8971091GSM8971092GSM8971093GSM8971094GSM8971095GSM8971096GSM8971097GSM8971075GSM8971098GSM8971076GSM8971077GSM8971099GSM8971078GSM8971079GSM8971080GSM8971081GSM8971082GSM8971083GSM8971103GSM8971104GSM8971105GSM8971084GSM8971085GSM8971086GSM8971087GSM8971088GSM8971100GSM8971089GSM8971101GSM89711021905721626296482Mus musculus