Corticosterone impairs dendritic cell maturation and function

Abstract

Summary Dendritic cells (DC) play a critical role in initiating and directing adaptive immune responses against pathogens and tumours. Immature DC are thought to act as sentinels in peripheral tissues where their main function is to capture antigen at sites of infection, whereas mature DC are highly efficient at priming T‐cell‐mediated immune responses against infectious pathogens. The DC maturation process is thought to be an important step in the efficient generation of cytotoxic T lymphocytes (CTL). It is well established that many aspects of immune function, including CTL‐mediated antiviral immunity, are modulated by neuroendocrine‐derived products. Corticosterone (CORT), an adrenal hormone produced at increased concentrations during a stress response, has been shown to play a role in impaired CTL responses in stressed animals, leading to high mortality in mice normally resistant to viral infection. While direct effects of neuroendocrine mediators on CTL have been studied, little is known about their effects on DC that are critical for CTL priming. Here, we found that physiologically relevant concentrations of CORT, acting via the glucocorticoid receptor, functionally compromise DC maturation. DC exposed to CORT remained phenotypically and functionally immature after stimulation with lipopolysaccharide and were impaired for the production of interleukin (IL)‐6, IL‐12, and tumour necrosis factor‐α. These effects were biologically significant, as CORT treatment resulted in a marked reduction in the ability of DC to prime naive CD8+ T cells in vivo. These findings offer a potential mechanism underlying stress‐associated immunosuppression.

β2-Adrenoreceptor Agonist Inhibits Antigen Cross-Presentation by Dendritic Cells

“…The effect of stress on the immune system is not only glucorticoid-mediated but also adrenergic-mediated (45,46). Both systems have shown a capacity to modulate the cross-presentation capability of DC (7,47,48), consistent with the deleterious effect of chronic stress on immune responses. However, b-agonists and antagonists are among the most widely used drugs in clinical practice for a number of distinct pathologies, including heart failure, hypertension, asthma, and migraines.…”

Glucocorticoid receptor translational isoforms underlie maturational stage-specific glucocorticoid sensitivities of dendritic cells in mice and humans

“…13,14,16,17 In addition, glucocorticoids may reduce the number of DCs via inhibiting DC migration and increasing DC apoptosis, 7,9,10,12,15,[18][19][20][21][22][23][24][25] although some other reports suggest that glucocorticoids do not induce DCs apoptosis. 13,16,26,27 It is not known whether different DC subsets have differential sensitivity to glucocorticoid-induced apoptosis.…”

Differential Modulation of TLR3- and TLR4-Mediated Dendritic Cell Maturation and Function by Progesterone

“…Consequently, glucocorticoids have been shown to limit the capacity of monocytes to develop into DCs, reduce Ag uptake, upregulate adhesion molecule expression, downregulate maturation markers, such as CD40, CD80, CD86, and MHC class II, inhibit production of proinflammatory cytokines including IL-1a, IL-1b, IL-6, IL-12p70, IFN-g, and TNF-a, reduce Ag presentation via the MHC class II pathway, and downmodulate T cell stimulatory capacity (16)(17)(18)(19)(20)(21)(22).…”