Extracellular vesicles released by triiodothyronine-stimulated dendritic cells induce a pro-inflammatory profile of allogenic murine splenocytes

NEGRETTI BORGA, DANA MARÍA; ALAMINO, VANINA ALEJANDRA; SOLER, MARÍA FLORENCIA; BRAVO MIANA, ROCÍO M.; BLANCO, ANTONELLA; DONADIO, ANA CAROLINA; MONTESINOS, MARÍA DEL MAR; PELLIZAS, CLAUDIA G

Congreso; 19th International Congress of Endocrinology (ICE); 2021

ISE, FELAEN and FASEN.

Introduction: The relationship between the neuroendocrine and immune systems is essential for homeostatic maintenance. We reported that physiological levels of triiodothyronine (T3) activate mice dendritic cells (DCs) through thyroid hormone receptors (TRβ), inducing Th1 and Th17 proinflammatory responses and restraining tolerogenic signals. These results were exploited with success in an antitumor DC-based vaccination protocol in vivo. Besides, we described that in vitro, nano-sized extracellular vesicles (EVs) released by T3-stimulated DCs (T3-DCs) activate syngeneic DCs, contributing to paracrine DC communication. However, the immune modulatory role of T3-DCs derived EVs on T cells is still unknown.Objectives: To evaluate the immune response induced by T3-DC released EVs in allogenic splenocytes.Methods: Bone marrow DCs obtained from C57BL/6 WT mice were stimulated (or not, control: C) with T3 (10nM) for 18h. DC-secreted EVs (DCs-EVs) were isolated by differential ultracentrifugation of the supernatant (2,000g: 2K; 10,000g: 10K; and 100,000g: 100K). Allogenic splenocytes were obtained from BALB/c mice and stimulated with DC-EVs for 6 days. Proliferation, intracellular and secreted cytokine production were analyzed by flow cytometry and ELISA assays, respectively. Statistical analysis: Sidak´s multiple comparisons test. P