Triiodothyronine (T3) triggers a metabolic reprogramming on mice dendritic cells (DC)

BLANCO A; NEGRETTI BORGA, DM; PUENTES EN; TEIXEIRA MP; DONADÌO AC; MONTESINOS MM; PELLIZAS CG

Mar del Plata

Congreso; LXVII Reunión Anual de la Sociedad de Investigación Clínica (SAIC); 2022

SAIC

Previous studies from our group 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 itsTLR-driven maturation, favoring glycolysis over oxidative phosphorylation (OXPHOS) and 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 the effects of T3 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 higher levels of iNOS (p<0.01), but it was not detected in iDC. Nitrite levels, indicative of NO production, were increased inT3-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 under course is designed to go in-depth with the understanding of the DC´s metabolic reprogramming induced by T3.