Triiodothyronine-stimulated dendritic cells promote a pro-inflammatory adaptive immune response ? in vivo evidences

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

Rio de Janeiro

Congreso; XVI Congress of the Latin American Thyroid Society; 2017

Latin American Thyroid Society (LATS)

Introduction: The immune and endocrine systems are in constant communication to maintain homeostasis and orchestratecoordinated 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 DCsand their ability to direct adaptive responses towards a Th1-type profile in vitro, as well as cytotoxic and antitumoral effects inan in vivo model of B16 melanoma. Furthermore, in vitro, T3 stimulated DC production of the Th17-skewing cytokines andreduced the expression of programmed death-ligand 1 and 2 (PD-L1 and PD-L2). In addition, T3-matured DCs increased theproduction of IL-17 and decreased the frequency of regulatory T (Treg) cells in allogenic splenocytes. Objectives: The aim ofthis study was to analyze the adaptive immune response induced by T3-stimulated DCs in vivo regarding in vitro findings andprevious therapeutic implications registered by T3-conditioned DC vaccination. Methods: Mice bone marrow derived DCstreated with ovalbumin (OVA) and 5 nM T3 (OVA+T3-DCs) for 18 h, were injected i.v. into OTII transgenic mice, whichown a four-fold increase in CD4/CD8 peripheral T cell ratio that primarily recognize OVA peptide (OVA323) when presentedby the MHC class II molecule. One week later, splenocytes were restimulated ex vivo with OVA323, and proliferation, IL-17and IFN-γ releases, and CD4+CD25+FoxP3+ (Tregs) and programmed death-1 protein (PD-1)+ cells were determined 4 dayslater by MTT assay, ELISA and FACS, respectively. Statistics: ANOVA/SNK test. Results: In OVA+T3-DCs treated mice wedemonstrated an increase in splenocytes proliferation and that spleen cells secrete higher IL-17 and IFN-γ levels vs. OVA-DCsinjected mice. In contrast, splenocytes from OVA+T3-DCs group decreased Treg population and exhibited a reduction of theexpression 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 DCsfavor the promotion of adaptive immunity towards a pro-inflammatory profile in vivo. Our findings have therapeutic implicationsfor the manipulation of the immunogenic potential of DCs to positively regulate the development of protective immunityor negatively control the generation of autoimmune diseases.