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.
Subject(s)
Adrenal Cortex Hormones/metabolism , Brain/immunology , Stress, Psychological/metabolism , Adrenal Cortex Hormones/cerebrospinal fluid , Adrenal Cortex Hormones/immunology , Animals , Behavior, Animal , 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 , T-Lymphocytes/immunologyABSTRACT
Vitamin D deficiency is common in the general population and even more frequent in patients with chronic diseases. The prevention of rickets with native vitamin D supplementation is one of the oldest and most effective prophylactic measures ever reported in medicine, leading to an almost complete eradication of vitamin D-deficient rickets in developed countries. We report on two children with vitamin D abnormalities: the first, 10-year-old child developed rickets without any vitamin D supplementation despite different risk factors (autism, ethnicity, nutritional problems, chronic antiepileptic therapies). In contrast, the second, 8-month-old child received double doses of native vitamin D from birth for several months and was referred for acute and symptomatic hypercalcemia. As such, vitamin D supplementation must follow specific rules: neither too much nor too little! We also discuss the emergence of "new" genetic diseases such as mutations in the 24-hydroxylase (CYP24A1) gene inducing neonatal hypercalcemia and nephrocalcinosis: we believe that before prescribing conventional vitamin D supplementation as recommended by the national guidelines, pediatricians should quickly rule out a potential genetic abnormality in phosphate/calcium metabolism (namely a history of lithiasis or hypercalcemia) that would lead to further biological investigations.
