Triiodothyronine (T3)-stimulated dendritic cells (DCs) promote a pro-inflammatory adaptive immune response ? In vivo evidences

RABINOVICH GA; SOLER MF; PELLIZAS CG; GIUSIANO L; ALAMINO VA; GIGENA N; MONTESINOS, MM

Rìo de Janeiro

Congreso; XVI Congreso Latinoamericano de Tiroides (LATS); 2017

Sociedad Latinoamericana de Tiroides

Introduction: The immune and endocrine systems are in constant communication to maintain homeostasis and orchestrate coordinated responses to imbalances and pathologies. In this sense, we previously reported that mice DCs, the main antigen-presenting cells, express thyroid hormone receptor β1 and that physiological levels of T3 stimulate the maturation of DCs and their ability to direct adaptive responses towards a Th1-type profile in vitro, as well as cytotoxic and antitumoral effects in an in vivo model of B16 melanoma. Furthermore, in vitro, T3 stimulated DC production of the Th17-skewing cytokines and reduced the expression of programmed death-ligand 1 and 2 (PD-L1 and PD-L2). In addition, T3-matured DCs increased the production of IL-17 and decreased the frequency of regulatory T (Treg) cells in allogenic splenocytes. Objectives: The aim of this study was to analyze the adaptive immune response induced by T3-stimulated DCs in vivo regarding in vitro findings and previous therapeutic implications registered by T3-conditioned DC vaccination. Methods: Mice bone marrow derived DCs treated with ovalbumin (OVA) and 5 nM T3 (OVA+T3-DCs) for 18 h, were injected i.v. into OTII transgenic mice, which own a four-fold increase in CD4/CD8 peripheral T cell ratio that primarily recognize OVA peptide (OVA323) when presented by the MHC class II molecule. One week later, splenocytes were restimulated ex vivo with OVA323, and proliferation, IL-17 and IFN-γ releases, and CD4+CD25+FoxP3+ (Tregs) and programmed death-1 protein (PD-1)+ cells were determined 4 days later by MTT assay, ELISA and FACS, respectively. Statistics: ANOVA/SNK test. Results: In OVA+T3-DCs treated mice we demonstrated an increase in splenocytes proliferation and that spleen cells secrete higher IL-17 and IFN-γ levels vs. OVA-DCs injected mice. In contrast, splenocytes from OVA+T3-DCs group decreased Treg population and exhibited a reduction of the expression of the inhibitory molecule PD-1, compared to those from OVA+DCs-treated mice. Conclusions and discussion: These results reinforce the critical role of T3 in the regulation and maintenance of immune homeostasis since T3-exposed DCs favor the promotion of adaptive immunity towards a pro-inflammatory profile in vivo. Our findings have therapeutic implications for the manipulation of the immunogenic potential of DCs to positively regulate the development of protective immunity or negatively control the generation of autoimmune diseases.