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

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

Victoria

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

American Thyroid Association (ATA)

The immune and endocrine systems are in constant communicationto maintain homeostasis and orchestrate coordinated responsesto imbalances and pathologies. In this sense, we reportedthat mice DCs, the main antigen-presenting cells, express thyroidhormone receptor b1 and that physiological levels of T3 stimulatethe maturation of DCs and their ability to direct a Th1-type immuneresponse in vitro, as well as antitumoral effects in an in vivomodel of melanoma. Furthermore, in vitro, T3 stimulated DC?sproduction of the Th17-skewing cytokines and reduced the expressionof programmed death-ligand 1 and 2 (PD-L1 and PD-L2). Inaddition, T3-matured DCs increased the production of IL-17 anddecreased the frequency of regulatory T (Treg) cells in allogenicsplenocytes. Regarding the in vitro findings, the aim of this studywas to analyze the adaptive immune response induced by T3-stimulated DCs in vivo. For this purpose, mice bone marrowderived DCs treated with ovalbumin (OVA) and 5 nM T3 (OVA+T3-DCs) for 18 h, were injected i.v. into OTII transgenic mice, whichown an increase in CD4/CD8 peripheral T cell ratio that primarilyrecognize OVA peptide (OVA323) when presented by the MHC classII molecule. One week later, splenocytes were restimulated ex vivowith OVA323, and proliferation, IL-17 and IFN-c releases, andCD4+CD25+FoxP3+ (Tregs) and programmed death-1 protein (PD-1)+ cells were determined 4 days later by MTT assay, ELISA andFACS, respectively. Statistics: ANOVA/SNK test. We observed anincrease in proliferation and IL-17 and IFN-c production in splenocytesfrom OVA+T3-DCs vs OVA-DCs treated mice. In contrast,spleen cells from OVA+T3-DCs group exhibited a reductionof Treg population and expression of the inhibitory molecule PD-1,compared to those from OVA+DCs-treated mice. These resultsreinforce the critical role of T3 in the regulation and maintenanceof immune homeostasis since T3-exposed DCs favor the promotionof adaptive immunity towards a pro-inflammatory profile in vivo.Our findings have therapeutic implications for the manipulation ofthe immunogenic potential of DCs to positively regulate the developmentof protective immunity or negatively control the generationof autoimmune diseases.