Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells

Nov 8, 2011Steroids

Dexamethasone reduces the immune-boosting effects of thyroid hormone (T3) on immune helper cells

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Dexamethasone inhibited T3-induced stimulation of dendritic cells by preventing the expression of maturation markers and IL-12 secretion.

Glucocorticoids may suppress the immunostimulatory effects of triiodothyronine on dendritic cells.
Dexamethasone increased IL-10 levels in T3-conditioned dendritic cells, suggesting a shift towards anti-inflammatory responses.
The inhibition of T3-matured dendritic cells resulted in reduced naive T-cell proliferation and decreased IFN-γ production.
Mechanistic analysis showed that dexamethasone modulated Akt activation and the movement of nuclear factor-κB between the cytoplasm and nucleus.
Dexamethasone decreased the expression of thyroid hormone receptor β1 in both immature and T3-matured dendritic cells.

AI simplified

Glucocorticoids (GCs) are widely used as anti-inflammatory and immunosuppressive agents. Several studies have indicated the important role of dendritic cells (DCs), highly specialized antigen-presenting and immunomodulatory cells, in GC-mediated suppression of adaptive immune responses. Recently, we demonstrated that triiodothyronine (T3) has potent immunostimulatory effects on bone marrow-derived mouse DCs through a mechanism involving T3 binding to cytosolic thyroid hormone receptor (TR) β1, rapid and sustained Akt activation and IL-12 production. Here we explored the impact of GCs on T3-mediated DC maturation and function and the intracellular events underlying these effects. Dexamethasone (Dex), a synthetic GC, potently inhibited T3-induced stimulation of DCs by preventing the augmented expression of maturation markers and the enhanced IL-12 secretion through mechanisms involving the GC receptor. These effects were accompanied by increased IL-10 levels following exposure of T3-conditioned DCs to Dex. Accordingly, Dex inhibited the immunostimulatory capacity of T3-matured DCs on naive T-cell proliferation and IFN-γ production while increased IL-10 synthesis by allogeneic T cell cultures. A mechanistic analysis revealed the ability of Dex to dampen T3 responses through modulation of Akt phosphorylation and cytoplasmic-nuclear shuttling of nuclear factor-κB (NF-κB). In addition, Dex decreased TRβ1 expression in both immature and T3-maturated DCs through mechanisms involving the GC receptor. Thus GCs, which are increased during the resolution of inflammatory responses, counteract the immunostimulatory effects of T3 on DCs and their ability to polarize adaptive immune responses toward a T helper (Th)-1-type through mechanisms involving, at least in part, NF-κB- and TRβ1-dependent pathways. Our data provide an alternative mechanism for the anti-inflammatory effects of GCs with critical implications in immunopathology at the cross-roads of the immune-endocrine circuits.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief