Triiodothyronine (T3)-stimulated dendritic cells (DCs) induce a pro-inflammatory adaptive response in vivo

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

Mar del Plata

Congreso; LXIV Reunión Científica Anual de la Sociedad Argentina de Inmunología (SAI), LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC), XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE); 2016

We previously reported that mice DCs, the main antigenpresentingcells, 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 restimulatedex 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 specific 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 adaptiveimmunity towards a pro-inflammatory profile. Our findingsmay be exploited to manipulate the immunogenic potential of DCsto positively regulate the development of protective immunity ornegatively control the generation of autoimmune diseases.