Dexamethasone affects day/night development and function of thymus-derived T regulatory cells

Thymus-derived T regulatory (tTregs) cells play a crucial role in the maintenance of tolerance and immune homeostasis. Mechanisms and factors regulating tTreg development and function are widely investigated, but to a large degree still remain unclear. Our previous findings demonstrated that, in physiological conditions, the development and suppressive function of tTregs demonstrated day/night rhythmicity, which correlated with the concentration of plasma corticosterone and the expression of glucocorticoid receptors. In this study we ask whether synthetic glucocorticoids commonly used to inhibit excessive activity of the immune system, can modulate the development and suppressive function of tTregs in vivo depending on the time of administration. Young C57BL/6 male and female mice were injected intraperitoneally with a single dose of dexamethasone at two time points of the day: 7.00-8.00 a.m. and 7.00-8.00 p.m. The experimental can be used to indicate on the potentially expected positive or adverse side effects and can constitute also a good model for the assessment of the effects of long-term therapy. The results of our studies demonstrated the increase of the percentage of tTregs at both time points in male mice, but only in the evening in females. The suppressive activity of tTregs increased independently on the day time of in female mice, but in the morning only in males. We concluded that in the condition of dexamethasone supplementation, the elevated suppressive potential of tTregs is balanced by the induction apoptosis in order to prevent excessive suppression.