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

BLANCO A; NEGRETTI-BORGA D; PUENTES E; PIRES TEXEIRA M; DONADIO AC; MONTESINOS MM; PELLIZAS CG

Mar del Plata

Congreso; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC). LXX Reunión Anual de la Sociedad Argentina de Inmunología (SAI).; 2022

Sociedad Argentina de Investigación Clínica

Our group previously demonstrated that T3 triggers adaptive pro-inflammatory and cytotoxic responses through DC activation, restraining regulatory signals. These results were successfully exploited inT3-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 controlledby different time-dependent pathways. Sustained commitment toglycolysis 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 effectson DC’s metabolic programming. Immature bone marrow derivedDC (iDC) were obtained from C57BL/6 mice and stimulated (or not)with T3 (10nM) for different time points. Glucose and lactate weremeasured in culture’s supernatants (SN) from iDC and T3-DC withcommercial kits. Glucose uptake was evaluated using the glucoseanalog 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 asignificant 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 higherGlut-1 expression than iDC. T3-DC expressed high levels of iNOS(p<0.01), but it was not detected in iDC. Nitrite levels, indicativeof NO production, were increased in T3-DC vs iDC (p<0.05). Thisstudy gives the first insights into the impact of T3 on DC’s metabolism, focusing on the glycolytic pathway. Further research is undercourse to go in-depth with the understanding of the DC´s metabolicreprogramming induced by T3.