INVESTIGADORES
SUSPERREGUY Sebastian
congresos y reuniones científicas
Título:
TRIIODOTITONINE (T3) STIMULATES DENDRITIC CELL FUNCTION THROUGH A PI3K-INDEPENDENT AKT PATHWAY: CRUCIAL ROL OF THYROID HORMONE RECEPTOR Β1, A NEW NF-ΚB TARGET GENE
Autor/es:
MASCANFRONI ID; MONTESINOS MM; ALAMINO VA; SUSPERREGUY S; NICOLA JP; MASINI-REPISO AM; RABINOVICH G; PELLIZAS CG
Lugar:
Gramado, Brasil. Mayo 2009.
Reunión:
Congreso; XII Congreso de la Sociedad Latinoamericana de Tiroides (LATS); 2009
Resumen:
We
demonstrated that mice dendritic cells (DC), the main antigen presenting cells,
express TRb1 with a preferential cytoplasmic
localization. Moreover, physiological levels of T3 stimulated DC maturation, strengthened their T cell allostimulatory
capacity and directed a T1-type cytokine response, involving cytoplasmic-nuclear
shuttling of NF-kB. In this study we aimed at disclosing the signaling pathway
involved in T3 action on DC and the role of TRb1 in these
effects. In turn we evaluated T3 effect on TRb1 expression
in DC and tested TRb1 gene as a
putative target of NF-kB. Bone marrow derived DC were treated with T3 (5nM) for
5 min to 18 h. Western blot of Akt/pAkt with or without PI3K inhibitors, co-immunoprecipitation,
immunofluorescence and confocal microscopies revealed for the first time the
involvement of the Akt pathway independently of PI3K in the recorded T3-induced
effects. In turn, experiments conducted with siRNA-TRb-transfected DC (TRb expression
abolished) prevented T3-induced DC maturation and function as well as Akt
activation and IkBe degradation,
demonstrating a crucial role of TRb1 in T3
effects at DC level. In turn, T3 increased TRb1 expression
in DC by a mechanism suppressed by NF-kB inhibitors. Chromatin
immunoprecipitation (ChIP) analysis revealed a new functional NF-kB consensus
site in the promoter region of TRb1 gene. Our
findings disclosed the molecular pathway involved in T3 effects on DC, through
a cytoplasmic signaling not previously described for T3 action and dependent on
TRb1; described TRb1 as a NF-kB target gene and also provided
tools to manipulate the immunogenic potential of DC.