TRIIODOTHYRONINE (T3) TRIGGERS A METABOLIC REPROGRAMMING ON MICE DENDRITIC CELLS (DC)

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencia, LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC).; 2022

Our group previously demonstrated that T3 triggers adaptive pro-inflammatory and cytotoxic responses through DC activation, restraining regulatory signals. These results were successfully exploited in T3-stimulated DC (T3-DC)-based antitumor vaccines against melanoma and colon carcinoma in mice. It is known that metabolic reprogramming of DC supports its TLR-driven maturation, favoring glycolysis over oxidative phosphorylation (OXPHOS), and is controlled by different time-dependent pathways. Sustained commitment to glycolysis relays on OXPHOS inhibition caused by nitric oxide (NO) produced by inducible NO Synthase (iNOS). On this basis, and given the potential of T3-DC vaccines, our aim was to assess T3 effects on DC?s metabolic programming. Immature bone marrow derived DC (iDC) were obtained from C57BL/6 mice and stimulated (or not) with T3 (10nM) for different time points. Glucose and lactate were measured in culture?s supernatants (SN) from iDC and T3-DC with commercial kits. Glucose uptake was evaluated using the glucose analog fluorescent dye 2-NBDG by FACS. Glucose transporter 1 (Glut-1) and iNOS expression were analyzed by Western Blot. Nitrite levels in SN were measured by the Griess reaction. Statistical analysis: t test or t test with Welch?s correction, p<0.05 was considered statistically significant. Compared to iDC, T3-DC showed a significant time-dependent increase in glucose consumption. Lactate production was also augmented in T3-DC (p<0.01). Besides, T3-DC exhibited a significant increase in glucose uptake and higher Glut-1 expression than iDC. T3-DC expressed high levels of iNOS (p<0.01), but it was not detected in iDC. Nitrite levels, indicative of NO production, were increased in T3-DC vs iDC (p<0.05). This study gives the first insights into the impact of T3 on DC?s metabolism, focusing on the glycolytic pathway. Further research is under course to go in-depth with the understanding of the DC´s metabolic reprogramming induced by T3.