Nuclear factor (NF)-kB-dependent thyroid hormone receptor β1-expression controls dendritic cell function via AKT signaling

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

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Lugar: Bethesda, Maryland; Año: 2010 vol. 285 p. 9569 - 9569

In spite of considerable progress in our understanding of the interplay betweenimmune and endocrine systems, the role of thyroid hormones and their receptorsin the control of adaptive immunity is still uncertain. Here we investigated therole of thyroid hormone receptor (TR) signaling in modulating dendritic cell(DC) physiology and the intracellular mechanisms underlying theseimmunoregulatory effects. Exposure of DCs to triiodothyronine (T3) resulted inrapid and sustained increase in Akt phosphorylation independently of PI3Kactivation, which was essential for supporting T3-induced DC maturationand IL-12 production. This effect was dependent on intact TR1 signaling assiRNA-mediated silencing of TR1 expression prevented T3-induced DCmaturation and IL-12 secretion as well as Akt activation and IB- degradation. Inturn, T3 up-regulated TR1 expression through mechanisms involving NF-B,suggesting an autocrine reg