Abstract
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 Gata3- and Foxp3-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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adrenal Cortex Hormones / cerebrospinal fluid
-
Adrenal Cortex Hormones / immunology
-
Adrenal Cortex Hormones / metabolism*
-
Animals
-
Behavior, Animal
-
Brain / immunology*
-
Brain / metabolism
-
Choroid Plexus / metabolism
-
Choroid Plexus / physiopathology
-
Epithelial Cells / immunology
-
Epithelial Cells / metabolism
-
Forkhead Transcription Factors / genetics
-
Forkhead Transcription Factors / metabolism
-
GATA3 Transcription Factor / metabolism
-
Hormone Antagonists / pharmacology
-
Humans
-
Mice, Inbred C57BL
-
Mice, Mutant Strains
-
Mifepristone / pharmacology
-
Receptors, Glucocorticoid / genetics
-
Receptors, Glucocorticoid / metabolism
-
Signal Transduction
-
Single-Cell Analysis
-
Stress, Psychological / immunology
-
Stress, Psychological / metabolism*
-
T-Lymphocytes / immunology
Substances
-
Adrenal Cortex Hormones
-
Forkhead Transcription Factors
-
Foxp3 protein, mouse
-
GATA3 Transcription Factor
-
Gata3 protein, mouse
-
Hormone Antagonists
-
Receptors, Glucocorticoid
-
Mifepristone