GALECTIN-1 INSTRUCTS THE DIFFERENTIATION OF REGULATORY DENDRITIC CELLS WITH TOLEROGENIC POTENTIAL IN AUTOIMMUNITY AND CANCER

J. ILARREGUI; G. BIANCO; M. VERMEULEN; M. TOSCANO; D. CROCI; J. GEFFNER; G. RABINOVICH

RIO DE JANEIRO

Congreso; 13TH INTERNATIONAL CONGRESS OF IMMUNOLOGY; 2007

ICI 2007

Galectin-1 instructs the differentiation of regulatory dendritic cells (DC) with tolerogenic potential in cancer and autoimmunity J.M. Ilarregui,1 G. Bianco,1 M. Vermeulen,2 M.A. Toscano,1 D.O. Croci,1 J. Geffner,2 G.A. Rabinovich1   1Lab Inmunogenética, Facultad de Medicina, UBA and 2IIHEMA, Academia Nacional de Medicina. Argentina   We have recently demonstrated that galectin-1 plays a role in immunoregulation and tumor-immune escape. Yet, the cellular mechanisms involved in this effect are still obscure. Here, we evaluated the impact of galectin-1 on the physiology of monocyte-derived human DC (MoDC) and bone marrow-derived murine DC (BMDC). Addition of galectin-1 to cultures of human monocytes resulted in a dose-dependent inhibition of immature DC differentiation. Moreover, MoDC maturated with LPS in the presence of galectin-1 suppressed mixed leukocyte reactions (MLRs) stimulated with control DC and modulated the IFN-g/IL-10 ratio (p<0.01) in a dose-dependent manner. A mechanistic analysis revealed an increased activation of the STAT3 pathway, with no evidence of apoptosis or induction of FoxP3+ Tregs. However. BMDC differentiated in the presence of galectin-1 (Gal-1-BMDC) showed a regulatory phenotype reflected by their ability to suppress an antigen-specific T-cell responses in vivo (p<0.05). In addition, Gal-1-BMDC were unable to protect against challenge with B16 melanoma compared to control DC (p<0.05). Furthermore, treatment of MOG35-55-induced Experimental Autoimmune Encephalomyelitis (EAE) with Gal-1-BMDC resulted in reduced clinical and pathological severity with higher levels of IL-10 (p<0.001). Finally, investigation of BMDC from gal-1-/- mice revealed higher MHC II expression upon maturation and significantly higher capacity to stimulate MLRs (p<0.05) than wt mice. We conclude that Gal-1 plays a critical role in the generation of human and murine regulatory DC with tolerogenic potential in autoimmunity cancer.