Nuclear factor (NF)-{kappa}B-dependent thyroid hormone receptor {beta}1-expression controls dendritic cell function via AKT signaling

MASCANFRONI ID; MONTESINOS MD,; ALAMINO VA; SUSPERREGUY S; NICOLA JP; ILARREGUI JM; MASINI - REPISO AM; RABINOVICH GA; PELLIZAS CG

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Lugar: Baltimore; Año: 2010 vol. 285 p. 9569 - 9569

p>Despite considerable progress in our understanding of the interplay between immune and endocrine systems, the role of thyroid hormones and their receptors in the control of adaptive immunity is still uncertain. Here, we investigated the role of thyroid hormone receptor (TR) beta(1) signaling in modulating dendritic cell (DC) physiology and the intracellular mechanisms underlying these immunoregulatory effects. Exposure of DCs to triiodothyronine (T(3)) resulted in a rapid and sustained increase in Akt phosphorylation independently of phosphatidylinositol 3-kinase activation, which was essential for supporting T(3)-induced DC maturation and interleukin (IL)-12 production. This effect was dependent on intact TR beta(1) signaling as small interfering RNA-mediated silencing of TR beta(1) expression prevented T(3)-induced DC maturation and IL-12 secretion as well as Akt activation and I kappaB-epsilon degradation. In turn, T(3) up-regulated TR beta(1) expression through mechanisms involv