biostudies-literaturePark SNational Research Foundation of Korea (NRF)Institute for Basic Science (IBS)8330https://www.ebi.ac.uk/biostudies/studies/S-EPMC12454645biostudies-literatureUnknown16(1)Astrocytes are critical contributors to brain disorders, yet the mechanisms underlying their selective vulnerability to specific diseases remain poorly understood. Here, we demonstrate that NR3C1 acts as a key regulator of early postnatal astrocyte development, shaping long-term immune responses in mice. Through integrative analyses of gene expression, chromatin accessibility, and long-range chromatin interactions, we identify 55 stage-specific TFs, with NR3C1 uniquely associated with early postnatal maturation. Although mice lacking astrocytic NR3C1 exhibit no detectable developmental abnormalities, these mice display heightened susceptibility to exacerbated immune responses following adult-onset experimental autoimmune encephalomyelitis (EAE). Many of the dysregulated EAE response genes Nature communicationsNR3C1-mediated epigenetic regulation suppresses astrocytic immune responses in mice.PMC12454645IBS-R025-A1RS-2023-00223069RS-2023-002625272021R1A2C30057042022R1A5A10264132023R1A2C3002773Lee AJPark HJoo JDiao YByun YGJung IChung WSWei XPark SEom JfalseNR3C1-mediated epigenetic regulation suppresses astrocytic immune responses in mice.Astrocytes are critical contributors to brain disorders, yet the mechanisms underlying their selective vulnerability to specific diseases remain poorly understood. Here, we demonstrate that NR3C1 acts as a key regulator of early postnatal astrocyte development, shaping long-term immune responses in mice. Through integrative analyses of gene expression, chromatin accessibility, and long-range chromatin interactions, we identify 55 stage-specific TFs, with NR3C1 uniquely associated with early postnatal maturation. Although mice lacking astrocytic NR3C1 exhibit no detectable developmental abnormalities, these mice display heightened susceptibility to exacerbated immune responses following adult-onset experimental autoimmune encephalomyelitis (EAE). Many of the dysregulated EAE response genes 2025-01-01T00:00:00Z2025 Sep2026-06-03T19:05:11.541Z2026-04-30T03:11:52.02ZS-EPMC124546454098361510.1038/s41467-025-64088-5