CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Triiodothyronine (T3)-stimulated dendritic cells (DCs) induce a pro-inflammatory adaptive response in vivo.
Autor/es:
SOLER, MARÍA FLORENCIA; RABINOVICH GA; MONTESINOS, MARÍA DEL MAR; GIGENA, NICOLÁS; ALAMINO, VANINA A.; GIUSIANO, LUCILA; PELLIZAS, CLAUDIA G.
Lugar:
Mar del Plata, Buenos Aires, Argentina
Reunión:
Congreso; LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2016
Institución organizadora:
Sociedad Argentina de Investigación Clínica-Sociedad Argentina de Inmunología
Resumen:
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 immunehomeostasis 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.