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

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

We previously reported that mice DCs, the main antigenpresenting cells, express thyroid hormone receptor β1 and thatphysiological levels of T3 stimulate the maturation of DCs andthe ability to develop a Th1-type response in vitro (FASEB J2008,22:1032), as well as cytotoxic and antitumoral effects inan 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 theexpression of programmed death-ligand-1 (PD-L1). In addition,T3-matured DCs increased the production of IL-17 and decreasedthe frequency of Treg cells in allogenic splenocytes (Thyroid2015,25:S1). The aim of this study was to further analyze theimmune response induced by T3-stimulated DCs in vivo. For thispurpose, 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-βreleases, and CD4+CD25+FoxP3+ (Tregs) and PD1+ cells weredetermined 4 days later by MTT assay, ELISA and FACS, respectively. Results registered that OVA+T3-DCs treated mice increasedsplenocytes? proliferation and spleen cells secreted higher IL-17and IFN-β levels than those OVA-DCs injected mice, indicating thegeneration of a specifc immune response. Incontrast, splenocytesfrom OVA+T3-DCs group decreased Treg population and exhibiteda tendency towards a reduction of PD-1 expression compared tothose from OVA+DCs-treated mice. These results reinforce thecritical 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 profle. Our fndingsmay be exploited to manipulate the immunogenic potential of DCsto positively regulate the development of protective immunity ornegatively control the generation of autoimmune diseases.