Nuclear factor (NF)-κB-dependent thyroid hormone receptor β 1 expression controls dendritic cell function via Akt signaling

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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) β 1 signaling in modulati...

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Detalles Bibliográficos
Autores principales: Mascanfroni, I.D., Montesinos, M.D.M., Alamino, V.A., Susperreguy, S., Nicola, J.P., Ilarregui, J.M., Masini-Repiso, A.M., Rabinovich, G.A., Pellizas, C.G.
Formato: JOUR
Materias:
Adaptive immunity
AKT activation
Akt phosphorylation
Chromatin immunoprecipitation analysis
Dendritic cells
Endocrine systems
Mechanism control
Nuclear factors
Phosphatidylinositol 3-kinase
Promoter region
Small interfering RNA
Thyroid hormone receptor
Thyroid hormones
Activation analysis
Chemical activation
Dendrimers
Endocrinology
Hormones
Phosphorylation
Physiology
RNA
Signaling
Adaptive control systems
immunoglobulin enhancer binding protein
interleukin 12
liothyronine
phosphatidylinositol 3 kinase
protein kinase B
small interfering RNA
thyroid hormone receptor beta
thyroid hormone receptor beta 1
unclassified drug
animal cell
animal tissue
article
autocrine effect
cell function
cell maturation
chromatin immunoprecipitation
controlled study
cytokine production
dendritic cell
enzyme activation
enzyme phosphorylation
female
gene expression regulation
gene function
immunoregulation
mouse
nonhuman
priority journal
promoter region
signal transduction
upregulation
animal
C57BL mouse
immunoblotting
metabolism
phosphorylation
Animals
Dendritic Cells
Enzyme Activation
Female
Gene Expression Regulation
Immunoblotting
Interleukin-12
Mice
Mice, Inbred C57BL
NF-kappa B
Proto-Oncogene Proteins c-akt
RNA, Small Interfering
Signal Transduction
Thyroid Hormone Receptors beta
Triiodothyronine
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00219258_v285_n13_p9569_Mascanfroni
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario: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) β 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 TRβ 1 signaling as small interfering RNA-mediated silencing of TRβ 1 expression prevented T 3 -induced DC maturation and IL-12 secretion as well as Akt activation and IκB-ε degradation. In turn, T 3 up-regulated TRβ 1 expression through mechanisms involving NF-κB, suggesting an autocrine regulatory loop to control hormone-dependent TRβ 1 signaling. These findings were confirmed by chromatin immunoprecipitation analysis, which disclosed a new functional NF-κB consensus site in the promoter region of the TRB1 gene. Thus, a T 3 -induced NF-κB-dependent mechanism controls TRβ 1 expression, which in turn signals DCs to promote maturation and function via an Akt-dependent but PI3K-independent pathway. These results underscore a novel unrecognized target that regulates DC maturation and function with critical implications in immunopathology at the crossroads of the immune-endocrine circuits. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

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