In vivo evidences towards a pro-inflammatory immune response generated by trriodothyronine-stimulated dendritic cells (DCs)

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

Victoria

Congreso; 87th Annual Metting of the American Thyroid Association (ATA); 2017

American Thyroid Association (ATA)

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 a Th1-type immune response in vitro, as well as antitumoral effects in an in vivo model of melanoma. Furthermore, in vitro, T3 stimulated DC?s 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. Regarding the in vitro findings, the aim of this study was to analyze the adaptive immune response induced by T3-stimulated DCs in vivo. For this purpose, 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 an 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. We observed an increase in proliferation and IL-17 and IFN-γ production in splenocytes from OVA+T3-DCs vs OVA-DCs treated mice. In contrast, spleen cells from OVA+T3-DCs group exhibited a reduction of Treg population and expression of the inhibitory molecule PD-1, compared to those from OVA+DCs-treated mice. 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