biostudies-literatureKertser AEuropean Research Councileaav4111https://www.ebi.ac.uk/biostudies/studies/S-EPMC6541460biostudies-literatureUnknown5(5)The immune system supports brain plasticity and homeostasis, yet it is prone to changes following psychological stress. Thus, it remains unclear whether and how stress-induced immune alterations contribute to the development of mental pathologies. Here, we show that following severe stress in mice, leukocyte trafficking through the choroid plexus (CP), a compartment that mediates physiological immune-brain communication, is impaired. Blocking glucocorticoid receptor signaling, either systemically or locally through its genetic knockdown at the CP, facilitated the recruitment of <i>Gata3-</i> and <i>Foxp3</i>-expressing T cells to the brain and attenuated post-traumatic behavioral deficits. These findings functionally link post-traumatic stress behavior with elevated stress-related corticosteroid signaling at the brain-immune interface and suggest a novel therapeutic target to attenuate the consequences of severe psychological stress.Science advancesCorticosteroid signaling at the brain-immune interface impedes coping with severe psychological stress.PMC6541460232835Baruch KKenigsbuch MCooper IWeiner ATsoory MDeczkowska AKertser ASchwartz MAmit ICroese TBen-Hamo SfalseCorticosteroid signaling at the brain-immune interface impedes coping with severe psychological stress.The immune system supports brain plasticity and homeostasis, yet it is prone to changes following psychological stress. Thus, it remains unclear whether and how stress-induced immune alterations contribute to the development of mental pathologies. Here, we show that following severe stress in mice, leukocyte trafficking through the choroid plexus (CP), a compartment that mediates physiological immune-brain communication, is impaired. Blocking glucocorticoid receptor signaling, either systemically or locally through its genetic knockdown at the CP, facilitated the recruitment of <i>Gata3-</i> and <i>Foxp3</i>-expressing T cells to the brain and attenuated post-traumatic behavioral deficits. These findings functionally link post-traumatic stress behavior with elevated stress-related corticosteroid signaling at the brain-immune interface and suggest a novel therapeutic target to attenuate the consequences of severe psychological stress.2019-01-01T00:00:00Z2019 May2021-02-21T07:30:28Z2019-07-01T13:56:45ZS-EPMC65414603114963210.1126/sciadv.aav4111