THYROID HORMONE ACTION IN THE INITIATION OF THE IMMUNE RESPONSE: EFFECT OF TRIIODOTHYRONINE ON MICE DENDRITIC FUNCTION

MASCANFRONI I D; MONTESINOS MM; SUSPERREGUY S; CERVI L; MASINI- REPISO AM; ILARREGUI JM; RABINOVICH GA; PELLIZAS CG

Santiago de Chile, Abril 2007

Congreso; XI Congreso de la Sociedad Latinoamericana de Tiroides (LATS); 2007

A cross-talk between the endocrine and the immune systems was established. However, the role of thyroid hormones (TH) in the initiation of the immune response is still lacking. The majority of TH action is exerted through nuclear TH receptors (TR) although growing evidence supports the involvement of non-genomic pathways. The main antigen presenting cells are dendritic cells (DC) that stimulate naive T cells and initiate and regulate primary immune responses. In vitro, mice DC can be generated from bone marrow (immature DC: iDC) with a retained capability for uptaking and processing antigens. The exposure of iDC to pro-inflammatory stimuli (as lipopolysaccharide, LPS) generates mature DC able to stimulate T cells. Previously, we presented initial evidence for the presence of TR in DC. The aim of this study was to further characterize TR from DC, to evaluate the effect of T3 on DC function and to analyze the signalling pathway involved. Mice DC were cultured from bone marrow with GM-CSF for 7 days. Afterwards, DC were pulsed with LPS 10 µg/ml (DCLPS) or T3 500-0.05 nM (DCT3) for the final 18 h. After cell harvesting, TR were revealed by Western Blot of subcellular fractions and immunocytochemistry. DC surface phenotype was determined by flow cytometry and cytokine production by ELISA. The ability of DCT3 to stimulate T cells was assessed in a mixed lymphocyte reaction (MLR). Cytoplasmic-nuclear shuttling of nuclear factor kb (NFkb) was assessed by Western Blot. Results: 1) TR were expressed in DC mainly in the cytoplasm. 2) T3 induced a significant increase of: DC surface maturation markers (MHC-II, CD80, CD86 and CD40), IL-12 as well as INFg production and an allogenic T lymphocyte proliferative response. 3) The involvement of NFkb pathway was evidenced. Conclusions and Discussion: These results provide evidence for a positive effect of physiologic levels of T3 on mice DC activation, assessed by surface phenotype, cytokine production and functional properties, with the involvement of the NFkb signalling pathway. In agreement with other cell types reported, TR was mainly localized in the cytoplasm of DC.