Triiodothyronine-stimulated dendritic cells induce a pro-inflammatory adaptive response in vivo

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

Mar del Plata

Congreso; LXIV Reunión Científica Anual de la Sociedad Argentina de Inmunología; 2016

Sociedad Argentina de Inmunología (SAI)

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 the ability to develop a Th1-type response in vitro (FASEB J 2008,22:1032), as well as cytotoxic and antitumoral effects in an in vivo model of B16 melanoma (Cancer Res 2015,420:105). Furthermore, in vitro, T3 stimulated DC production of the Th17-skewing cytokines TGF-β, IL-6, IL-23 and IL-1β and reduced the expression of programmed death ligand-1 (PD L1). In addition, T3-matured DCs increased the production of IL-17 and decreased the frequency of Treg cells in allogenic splenocytes (Thyroid 2015,25:S1). The aim of this study was to further analyze the 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. One week later, splenocytes were restimulated ex vivo with OVA323, and proliferation, IL-17 and IFN-γ releases, and CD4+CD25+FoxP3+ (Tregs) and PD1+ cells were determined 4 days later by MTT assay, ELISA and FACS, respectively. Results registered that OVA+T3-DCs treated mice increased splenocytes? proliferation and spleen cells secreted higher IL-17 and IFN-γ levels than those OVA-DCs injected mice, indicating the generation of a specific immune response. In contrast, splenocytes from OVA+T3-DCs group decreased Treg population and exhibited a tendency towards a reduction of PD-1 expression 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. Our findings may be exploited to manipulate the immunogenic potential of DCs to positively regulate the development of protective immunity or negatively control the generation of autoimmune diseases.