Nuclear Factor (NF)-kappa B-dependent Thyroid Hormone Receptor beta 1 Expression Controls Dendritic Cell Function via Akt Signaling

IVAN D. MASCANFRONI; MONTESINOS MARÍA DEL MAR; ALAMINO VANINA ALEJANDRA; SEBASTIÁN SUSPERREGUY; JUAN NICOLA; JUAN ILARREGUI; ANA MARÍA MASINI DE REPISO; GABRIEL RABINOVICH; CLAUDIA GABRIELA PELLIZAS

JOURNAL OF BIOLOGICAL CHEMISTRY

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Año: 2010 vol. 285 p. 9569 - 9569

0021-9258

espite considerable progress in our understanding of theinterplay between immune and endocrine systems, the role ofthyroid hormones and their receptors in the control of adaptiveimmunity is still uncertain. Here, we investigated the role ofthyroid hormone receptor (TR) 1 signaling in modulating dendritic cell (DC) physiology and the intracellular mechanismsunderlying these immunoregulatory effects. Exposure of DCs totriiodothyronine (T3) resulted in a rapid and sustained increasein Akt phosphorylation independently of phosphatidylinositol3-kinase activation, which was essential for supporting T3-induced DC maturation and interleukin (IL)-12 production. Thiseffect was dependent on intact TR1 signaling as small interfering RNA-mediated silencing of TR1 expression preventedT3-induced DC maturation and IL-12 secretion as well as Aktactivation and IB- degradation. In turn, T3 up-regulatedTR1 expression through mechanisms involving NF-B, suggesting an autocrine regulatory loop to control ho