Abstract
In humans, numbers of circulating naive T cells strongly decline in the morning, which was suggested to be mediated by cortisol, inducing a CXCR4 up-regulation with a subsequent extravasation of the cells. As a systematic evaluation of this assumption is lacking, we investigated in two human placebocontrolled studies the effects of the glucocorticoid receptor (GR) antagonist mifepristone (200 mg orally at 23:00) and of suppressing endogenous cortisol with metyrapone (1 g orally at 04:00) on temporal changes in CXCR4 expression and numbers of different T-cell subsets using flow cytometry. Mifepristone attenuated, and metyrapone completely blocked, the morning increase in CXCR4 expression on naive T cells. In parallel, both substances also hindered the decline in naive T-cell numbers with this effect, however, being less apparent after mifepristone. We identified, and confirmed in additional in vitro studies, a partial agonistic GR effect of mifepristone at night (i.e., between 02:00 and 03:30) that could explain the lower antagonistic efficacy of the substance on CXCR4 expression and naive T-cell counts. CXCR4 expression emerged to be a most sensitive marker of GR signaling. Our studies jointly show that endogenous cortisol, specifically via GR activation, causes the morning increase in CXCR4 expression and the subsequent extravasation of naive T cells, thus revealing an important immunological function of the morning cortisol rise.
Original language | English |
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Journal | FASEB Journal |
Volume | 28 |
Issue number | 1 |
Pages (from-to) | 67-75 |
Number of pages | 9 |
ISSN | 0892-6638 |
DOIs | |
Publication status | Published - 01.01.2014 |
Research Areas and Centers
- Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)