| Title: |
Chronic exposure to stress predisposes to higher autoimmune susceptibility in C57 BL/6 mice: Glucocorticoids as a double‐edged sword |
| Authors: |
Harpaz, Idan; Abutbul, Shai; Nemirovsky, Anna; Gal, Ram; Cohen, Hagit; Monsonego, Alon |
| Source: |
European Journal of Immunology ; volume 43, issue 3, page 758-769 ; ISSN 0014-2980 1521-4141 |
| Publisher Information: |
Wiley |
| Publication Year: |
2013 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Stress activates the hypothalamic‐pituitary‐adrenocortical axis to promote the release of corticosterone ( CORT ), which consequently suppresses pathogenic stimulation of the immune system. Paradoxically, however, stress often promotes autoimmunity through yet unknown mechanisms. Here we investigated how chronic variable stress ( CVS ), and the associated alterations in CORT levels, affect the susceptibility to experimental autoimmune encephalomyelitis (EAE) in female and male C 57 BL /6 mice. Under baseline (nonstressed) conditions, females exhibited substantially higher CORT levels and an attenuated EAE with less mortality than males. However, CVS induced a significantly worsened EAE in females, which was prevented if CORT signaling was blocked. In addition, females under CVS conditions showed a shift toward proinflammatory T h1/ T h17 versus T h2 responses and a decreased proportion of CD 4 + CD 25 + T reg cells. This demonstrates that whereas C 57 BL /6 female mice generally exhibit higher CORT levels and an attenuated form of EAE than males, they become less responsive to the immunosuppressive effects of CORT under chronic stress and thereby prone to a higher risk of destructive autoimmunity. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1002/eji.201242613 |
| Availability: |
https://doi.org/10.1002/eji.201242613; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Feji.201242613; https://onlinelibrary.wiley.com/doi/pdf/10.1002/eji.201242613 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| Accession Number: |
edsbas.7F10AA7F |
| Database: |
BASE |