TRIIODOTHYRONINE (T3)-STIMULATED DENDRITIC CELLS (DCS) INDUCE A PRO-INFLAMMATORY ADAPTIVE RESPONSE IN VIVO.

Mar del Plata

Congreso; LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2016

Sociedad Argentina de Inmunología

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-β 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-β levels than those OVA-DCs injected mice, indicating the generation of a specific immune response. Incontrast, 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.