Immunomodulatory role of Sphingosine Kinase 1 (SK1) on Triiodothyronine (T3)-matured Dendritic Cells (DC) and the driven adaptive response

NEGRETTI- BORGA DANA MARÍA; BLANCO ANTONELLA; PIRES TEIXEIRA MARIANA; ALAMINO VANINA ALEJANDRA; SOLER MARÍA FLORENCIA; PUENTES ELIDA NAHIR; DONADIO ANA CAROLINA; CHRISTOPHER J. CLARKE; MONTESINOS MARÍA DEL MAR; YUSUF A. HANNUN; PELLIZAS CLAUDIA GABRIELA

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

SAIC - SAI - SAFIS

Our group demonstrated that T3 generates adaptive proinflammatory and cytotoxic responses throughDC activation, restraining regulatory signals. This protocol was successfully exploited in T3-stimulated DC(T3-DC)-based antitumor vaccines. T3 effects are mainly triggered by non-genomic mechanisms involvingthyroid hormone receptor, Akt and NF-kB. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipidproduced by SK1 and 2. Although this pathway is involved in many proinflammatory conditions, little isknown about its role in innate immune cells. We aim to evaluate the role of SK1 in T3-DC, and the drivenadaptive immunity. Bone marrow DC were obtained from C57BL/6 WT or SK1-KO mice and stimulated(or not) with T3 (10nM). PF-543 (SK1 inhibitor, 100nM) was added, and 30 min later the T3 stimuli (PF-T3-DC). After 30 min, p-Akt/total Akt was analyzed by Western Blot. Allogenic splenocytes isolated fromBALB/c mice were co-cultured with T3-DC or PF-T3-DC (exposed to T3 for 18h), for 3 days. Viability andproliferation were evaluated by FACS. Cytokines were measured by FACS and ELISA. Statistical analysis:Two-way ANOVA/Tukey test, and paired t test. p