Glucocorticoids (GC) are widely used as antiinflammatory and immunosuppressive agents in the therapy of many autoimmune and allergic diseases and in transplantation to prevent rejection. Several studies have indicated the important role of antigen-presenting cells(APC) in GC-mediated suppression of immunity. Among APC, dendritic cells (DC) are considered to be the most efficient and indispensable to stimulate naïve T cells and induce antigen-specific immune responses (Guermonprez et al., 2002). Given the remarkable plasticity of these cells, manipulation of their function to favor the induction of DC with immunogenic or tolerogenic properties could be exploited in order to stimulate or attenuate immune responses (Steinman & Banchereau, 2007). Mice DC are generated from bone marrow (immature DC:iDC) and the exposure to pro-inflammatory stimuli (lipopolysaccharide,LPS) generates mature DC (mDC) that stimulate T cells. We have provided evidence for thyroid hormone receptor (TR) b1 expression and triiodothyronine (T3) stimulatory action on DC (Mascanfroniet al, FASEB Journal, 2008) by a mechanism involving T3 binding to cytosolic TRb1 and a rapid and sustained Akt activation dependent on TRb1 and essential for supporting T3-induced DC maturation and IL-12 production (Mascanfroni et al., J BiolChem, 2010). Recently, we demonstrated that Dexamethasone (Dex: synthetic GC) reduced TRb1 expression in DC by a mechanism that involved the glucocorticoid receptor (GR) (Montesinos et al., Arquivos Brasileiros de Endocrinologia & Metabologia, 2009). The aim of this study was to further evaluate the effect of Dex on T3 action in DC and to analyze the signalling pathway involved. Mice DC were cultured from bone marrow with GM-CSF for 7 days. Afterwards, iDC were pulsed with Dex 10 nM, LPS 100 ng/ml (positive control) or T3 5 nM for 18 h. After cell harvesting, DC surface phenotype was determined by flow cytometry and cytokine production by ELISA. The ability of treated-DC to stimulate T cells was assessed in a mixed lymphocyte reaction (MLR). We measured Akt-phosphorylation by Western Blot. Results: 1) the increment in DCmaturation markers and IL-12-producing DC induced by T3 and LPS was abolished by Dex by a mechanism that involved GR (it was prevented by a GR antagonist: RU486). Besides, Dex increase IL-10 levels in DC maturated with T3 and LPS. 2) Dex abolished T3-effect inducing DC able to stimulate IL-10 and toinhibit INFg production by T cells in a MLR. 3) T3-induced Akt phosphorylation was inhibited by Dex. These results indicate that GC are able to act through GR on LPS and T3-activated DC by inhibiting production of the pro-inflammatory response by these cells. Moreover, GC prevent T cell activation induced by T3. As the present work demonstrates that Dex prevented Akt activation induced by T3 by a mechanism that may involvethe downregulation of TRβ1 induced by Dex, the findings achieved are of physiologic and therapeutic relevance as Akt activation has been shown to be of critical importance for promoting DC survival which is an essential requirement in DC-based tumor vaccines (Park et al., 2006). Hence, the use of GC in antitumor therapy should be reconsidered, mainly in specific protocols involving DC directed to tumor antigen.