Triiodothyronine regulation of adaptive immunity through extracelular vesicles released by dendritic cells

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

Virtual por pandemia sars-cov2

Congreso; XVIII Latin American Thyroid Congress 2021; 2021

Latin American Thyroid Congress

Triiodothyronine (T3) induces modifications of different components of the immune system network. We reported that mice Dendritic Cells (DCs), professional antigen-presenting cells, mature and become activated in the presence of T3 (T3-DCs). In co-culture, T3-DCs increase CD8+ cytotoxic T cells and drive to proinflammatory (Th1 and Th17) immune responses. Moreover, the administration of antigen-specific T3-DCs in antitumor vaccination strategies successfully reduced melanoma and colon cancer tumors in vivo. Extracellular vesicles (EVs) are nano-vesicles secreted by all cells. They are composed of lipids, proteins, and nucleic acids. They interact with specific target cells, modifying their functions. EVs secreted by DCs (DC-EVs) are able to drive an antigen-specific T cell activation. Moreover, EVs from IFN-γ-matured DCs promote a Th1 profile, and EVs released by LPS-matured DCs promote CD8+ T cell responses. We characterized EVs released by T3-matured DCs (T3-EVs) for the first time, and described their ability to induce functional syngeneic DCs activation, in vitro. Herein, we aim to evaluate the role of T3-EVs on the immune adaptive responses that were previously registered by T3-DCs, evaluating the effect of T3-EVs on allogenic splenocytes. Bone marrow DCs obtained from C57BL/6 WT mice were stimulated (or not, control: C) with T3 (10nM) for 18h. DC-EVs were isolated from culture medium by differential ultracentrifugation (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. Intracellular and secreted cytokine production were analyzed by flow cytometry and ELISA assays, respectively. Statistical analysis: Sidak´s multiple comparisons test. P<0.05 was considered statistically significant. Results shown that T3-100K and T3-2K EVs increased CD8+ frequency, and allogenic splenocyte responses in vitro (vs C-100K and C-2K, respectively). Furthermore, T3-2K increase the secretion of IFN-γ (p<0.001) and IL-17 (p<0.01) from splenocytes (vs C-2K). Similarly, T3-10K upregulated IL17 secretion (p<0.01; vs C-10K). In conclusion, T3-EVs activated naïve splenocytes with fraction dependence, revealing the results obtained after T3-DC/allogenic splenocyte co-cultures. Therefore, T3-EVs are involved in the amplification of thyroid hormone regulation of adaptative immunity. More studies will further enlighten the role of T3-DCs as regulators of adaptive the immune responses.