Glucocorticoids prevent thyroid hormone action at the level of the initiation of the immune response. Role of dexamethasone on triiodothyronine (T3) effects on mice dendritic cell characteristics

MONTESINOS MARÍA DEL MAR, MASCANFRONI IVAN DARÍO, ALAMINO VANINA ALEJANDRA, SUSPERREGUY SEBASTIÁN, ALAMINO VANINA ALEJANDRA, MASINI ANA MARÍA, RABINOVICH GABRIEL ADRÍAN Y PELLIZAS CLAUDIA GABRIELA

Gramado, Brasil

Congreso; XIII Annual meeting of Latin American Thyroid Society; 2009

Latin American Thyroid Society

Glucocorticoids (GC) modulate immune responses and are used for autoimune/inflammatory disorders. Several studies emphasized the role of antigen presenting cells (APC) in GC-mediated suppression of immunity. Dendritic cells (DC) are the main APC that stimulate naive T cells to regulate adaptive immunity. 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 demonstrated that GC enhance triiodothyronine (T3)-dependent actions in liver involving an increase of thyroid hormone receptor (TR)b1 expression (Montesinos et al. Life Sciences 78:2584,2006). Recently, we provided evidence for TRb1 expression and T3 stimulatory action on DC (Mascanfroni et al, FASEB Journal 22:1032,2008) by a mechanism involving T3 binding to cytosolic TRb1 and Akt activation (Pellizas et al. RAEM 45:25,2008). We aimed at evaluating the effect of Dexamethasone (Dex: synthetic GC) on T3 action in DC. Mice iDC were pulsed with Dex 10 nM, LPS 100 ng/ml (positive control) or T3 5 nM. We measured TRb1 expression and Akt-phosphorylation by Western Blot, and DC maturation markers (CD86-CD40) and intracellular IL-12 production by flow cytometry. Results indicated that Dex reduced TRb1 expression in iDC and mDC by a mechanism that involved GR (it was prevented by a GR antagonist: RU486). The increment in maturation markers and IL-12-producing DC induced by T3 and LPS was abolished by Dex and restored by RU486. T3-induced Akt phosphorylation was inhibited by Dex. These results indicate that GC and T3 mechanisms of action are interrelated in a tissue-specific manner.