DENDRITIC CELLS PLAY A CENTRAL ROLE IN THE PATHOGENESIS OF Yersinia enterocolitica-INDUCED REACTIVE ARTHRITIS IN TNFRp55 DEFICIENT MICE

ANDREA CONSTANZA MAYORDOMO ; JUAN EDUARDO SILVA; CAROLINA VIRGINIA GORLINO; JOSÉ LUIS ARIAS; WALTER BERÓN ; MARÍA SILVIA DI GENARO

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

SOCIEDADES DE BIOCIENCIAS

Dendritic cells (DC) orchestrate immune responses presentingantigens to T lymphocytes and driving their activation and differentiationto effector T cells. In previous studies, we demonstratedthat TNFRp55-deficient (TNFRp55-/-) mice develop reactive arthritis(ReA) after orogastric infection with Yersinia enterocolitica (Ye). Thepurpose of the present work was to study the contribution of DC inthe pathogenesis of Ye-induced ReA in this mouse model. The DCwere purified after their in vivo expansion by injection of Fms-liketyrosine kinase 3-Ligand (Flt3L)-transfected BL16 melanoma. IsolatedWT and TNFRp55-/- DC were stimulated with lipopolysaccharide(LPS), and IL-12/23p40 levels were assessed in culture supernatantsby ELISA. Moreover, these cells were in vitro infected with Ye,and then co-cultured with purified CD4+ T cells obtained from spleenof WT and TNFRp55-/- mice 5 days post-infection with Ye. After 5days, T cell differentiation to Th1 and Th17 profiles were analyzed byflow cytometry, and IFN-g and IL-17 levels were measured in culturesupernatants. We found that TNFRp55-/- DC secreted higher levelsof IL-12/23p40 compared with WT DCs (p