CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Thyroid hormone action on dendritic cells drives proinflamatory responses
Autor/es:
PELLIZAS CG
Lugar:
Beijing
Reunión:
Congreso; 17th International Congress of Immunology; 2019
Institución organizadora:
International Union of Immunology Societies (IUIS)
Resumen:
My area of expertise related to immunity lies in the impact of thyroid hormones (THs) on adaptive immunity through their effects on dendritic cell functioning.Some time ago, we reported that the expression of TH receptors (TRs) in mice dendritic cells (DCs) contributes to DC maturation and Th1-type cytokine secretion induced by the active TH: triiodothyronine, T3 (Mascanfroni et al., FASEB J 2008; 22:1032-42). At the molecular level, we found that these effects involve activation of Akt and NF-kB pathways that in turn upregulate TR expression (Mascanfroni et al., J Biol Chem 2010; 285:9569-82) and are counteracted by glucocorticoids (Montesinos et al., Steroids 2012; 77:67-76).Moreover, we identified a major role of T3 in induction of cytotoxic T cells and protection against melanoma tumor development via DC activation (Alamino et al., Cancer Research 2015, 75:1265-74, and Oncoimmunology 2016, 5:1-3). More recently, we provide initial evidence that T3 also improves mice colon cancer antitumor responses stimulated by DCs loaded with the own tumor antigens. With impact for future translation to oncotherapeutics, T3 stimulation of human DCs was provided (Soler at al., Arch Endocrinol Metab 2019, 63 (S2) S8, XVII Latinamerican Thyroid Congress, June 2019).On the other hand, we also provided support for a homoeostatic mechanism of the lack of effect of the main circulating TH, T4, on DC functionality. This report also described the mechanisms of TH transport across DC surface and TH metabolism in these cells, pivotal for TH action at target cell level (Gigena et al., J Endocrinol. 2017, 232:337-350). Recent initial results also suggest that extracellular vesicles released by DCs may be involved in the adaptive response induced by T3 exposure to DCs (Negretti-Borga et al. Arch Endocrinol Metab 2019, 63 (S2) S8, XVII Latinamerican Thyroid Congress, June 2019).In turn, we recently underscored an essential role for T3 in promoting a Th17-polarizing DC phenotype, favoring the differentiation of IL-17-producing gamma delta T-cells as well as hindering regulatory T cell responses. These effects were substantiated in vivo in antigen-specific responses in mice. (Alamino et al., Cellular Physiology and Biochemistry 2019, 52:354-367).A summary of recorded results of TH action in innate immunity, including the findings at DC level, was recently reported by my lab (Montesinos & Pellizas, Frontiers in Endocrinology 2019, 10:350).