Participation of Galectin-8 on dendritic cell activation

TRIBULATTI, MARÍA VIRGINIA; CARABELLI, JULIETA; CATTANEO, VALENTINA; CAMPETELLA, OSCAR

Los Cocos, Córdoba

Simposio; First Argentinean Spring Course in Advanced Immunology; 2013

Facultad de Ciencias Químicas, Universidad Nacional de Córdoba - Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI - CONICET)

Galectins (Gals), a family of mammalian lectins, have emerged as key regulators of the immune response. We found that Gal-1 and Gal-8 costimulated Ag-specific T cell responses, as evaluated in the DO11.10 TCROVA-transgenic mouse model, by acting simultaneously on antigen presenting cells (APCs) and target CD4 T cells. Remarkably, a single dose of recombinant Gal-1 or Gal-8 administered together with a suboptimal Ag dose to DO11.10 mice strengthened weak responses in vivo. These results raised the hypothesis that APCs could be activated after galectin binding. In fact, other groups have previously shown that Gal-1-treatment promoted dendritic cell (DC) maturation. Whether Gal-8 exerts a similar effect on these cells is still undetermined. After Gal-8 treatment, an increment of coestimulatory molecules expression (MHCII, CD80 and CD86) was observed by flow cytometry analysis, in primary bone marrow derived-DCs. Gal-8 also induced a mature/activated phenotype in these cells, as showed by F-actin labeling with conjugated phalloidin and fluorescence microscopy analysis. Moreover, the analysis of supernatans from Gal-8-treated DCs showed a marked increase of the pro-inflammatory cytokine, IL-6. Expression of endogenous Gal-8 in DCs was confirmed by western blot assays, and interestingly, an increased expression level of Gal-8 protein was found after activation with LPS. Participation of endogenous Gal-8 was also evidenced using bone marrow-derived DCs from Gal-8-/- mice. DCs from knockout mice were less responsive to LPS stimulation than those derived from control mice. Taken together, our results suggest that Gal-8 could be involved in DC maturation/activation process, which argues in favor of the participation of Gals in the initiation of adaptive immune response.