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.
| Original language | English |
|---|---|
| Article number | aav4111 |
| Number of pages | 15 |
| Journal | Science Advances |
| Volume | 5 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 29 May 2019 |
Funding
We thank G. Schütz and A. Chen for providing and assisting us with GR-floxed mice, O. Matcovitch-Natan for consulting on flow cytometry sorting techniques, and S. Schwarzbaum for editing the manuscript. Funding: This study was supported by Advanced European Research Council grants (232835), the Minerva Foundation, and an ISF Legacy BioMed grant (1353/15). A.D. is supported by Steven and Eden Romick. M.S. holds the Maurice and Ilse Katz Professorial Chair in Neuroimmunology. M.T. is the incumbent of the Carolito Stiftung Research Fellow Chair in Neurodegenerative Diseases. Author contributions: A.K. and K.B., in equal contribution and under the mentoring of M.S., conceived the general ideas of this study, performed all of the experiments, analyzed the data, and prepared the data for presentation. A.D., M.K., and T.C. assisted in experimental procedures. A.W. and I.A. assisted in analyzing data. I.C. assisted in transepithelial resistance recording experiments and subsequent data analysis. M.T. helped planning and assisted with all animal models. S.B.-H. assisted in intracerebroventricular injections. A.K., K.B., and M.S. wrote the manuscript. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.
All Science Journal Classification (ASJC) codes
- General
- Physics and Astronomy (miscellaneous)