A novel role for galectin-1 in the generation of regulatory dendritic cells

JUAN M. ILARREGUI, MÓNICA E. VERMEULEN, NATALIA RUBINSTEIN, MARTA A. TOSCANO, GERMÁN A. BIANCO, JORGE R. GEFFNER, GABRIEL A. RABINOVICH

Córdoba, Argentina

Congreso; VII Latin American Congress of Immunology; 2005

Latin American Society of Immunology

A NOVEL ROLE FOR GALECTIN-1 (GAL-1) IN THE GENERATION OF REGULATORY DENDRITIC CELLS (DC)   J ILARREGUI1, M VERMEULEN2, N RUBINSTEIN1, M TOSCANO1, G BIANCO1, J GEFFNER2, G RABINOVICH1   1LAB INMUNOGENETICA, FACULTAD DE MEDICINA, UBA & 2IIHEMA. ARGENTINA   We recently demonstrated that Gal-1 plays a major role in tumor-immune escape. In this study we evaluated the influence of Gal-1 in the physiology of monocyte-derived human DC and bone marrow-derived murine DC. Incorporation of Gal-1 during human or murine DC differentiation resulted in a dose-dependent inhibition of immature DC phenotype (p<0.05). This effect was also reflected by marked inhibition of the ability of Gal-1-treated DC (GalDC) to endocytose OVA and to stimulate T cell proliferation in MLR (p<0.05). Furthermore, when DC were matured in the presence of LPS and Gal-1, mature GalDC exhibited a regulatory phenotype, as shown by reduced IL-12 (p<0.05), increased IL-10 (p<0.05) and increased STAT3 phosphorylation. In addition, GalDC were able to inhibit a MLR stimulated with full competent DC in a dose-dependent manner with no evidence of cell apoptosis. This effect was accompanied by decreased IFN-g, increased IL-10 and upregulation of Foxp3. The regulatory phenotype was reflected by decreased ability of GalDC to elicit an antigen (OVA)-specific T cell response in vivo (p<0.05). The physiopathological relevance of this effect was confirmed by the reduced ability of GalDC to protect against challenge with B16 melanoma in vivo compared to control DC. We conclude that Gal-1 drives human and murine DC into regulatory DC with tolerogenic potencial, an effect which may critically influence tumor-immune escape.