Accumulating evidence indicates a functional cross-talk between immune and endocrine mechanisms in the modulation of innate and adaptive immune responses. However, the impact of thyroid hormones (TH) in the initiation of adaptive immunity has not yet been studied. Here we investigated the presence of thyroid hormone receptors (TR) and the impact of TH in the physiology of bone marrow-derived dendritic cells (DCs), specialized antigen-presenting cells with unique capacity to fully activate naïve T cells and orchestrate adaptive immunity. Both immature and lipopolysaccharide (LPS)-matured DC expressed TR at the mRNA and protein levels, showing a preferential cytoplasmic localization. Remarkably, physiological levels of triodothyronine (T3) stimulated the expression of DC maturation markers (MHC II, CD80, CD86 and CD40), markedly increased the secretion of IL-12 and stimulated the ability of DCs to induce naïve T cell proliferation and IFN-g production in allogeneic T cell cultures. Analysis of the mechanisms involved in these effects revealed the ability of T3 to influence the cytoplasmic-nuclear shuttling of nuclear factor-k B (NF-kB) on primed DCs. Our study provides the first evidence for the presence of TR on bone marrow-derived DCs and the ability of TH to regulate DC maturation and function. These results have profound implications in immunopathology, including cancer and autoimmune manifestations of the thyroid gland at the cross-road of immune and endocrine systems.
