Thyroid hormone action in the initiation of the immune response: effect of triiodothyronine (T3) on mice dendritic cell function

MASCANFRONI ID; MONTESINOS MM; SUSPERREGUY S; CERVI L; ILARREGUI J; MASINI-REPISO AM; RABINOVICH GA; PELLIZAS CG

Santiago de Chile

Congreso; XII Latin American Thyroid Congress; 2007

Latin American Thyroid Society

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 TH on DC functionality 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 (DC_LPS) or triiodothyronine (T3: 100-0.01 nM, DC_T3) for the final 18 h. After cell harvesting, TR were revealed by immunocytochemistry and Western Blotting of cellular fractions. DC surface phenotype was determined by flow cytometry and cytokine production by ELISA. The ability of DC_T3 to stimulate T cells was assessed in a mixed lymphocyte reaction (MLR). 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, CD40), IL-12 as well as INFg production and a T allogenic response. 3) the involvement of nuclear factor kb (NFkb) pathway was evidenced. Conclusions and Discussion: These results provide evidence for a positive effect of physiologic levels of T3 on 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 were mainly localized in the cytoplasm of DC.