Endogenous galectin-1 fine-tunes the tolerogenic function of dendritic cells

ILARREGUI JM; CROCI DO; SALATINO M; TOSCANO MA; VERMEULEN M; GEFFNER JR; RABINOVICH GA

Viña del Mar, Chile.

Congreso; 9th Latin-American Congress of Immunology; 2009

Latin-American Association of Immunology

619 Endogenous galectin-1 fine-tunes the tolerogenic function of dendritic cells Juan Martín Ilarregui1, Diego Omar Croci1, Mariana Salatino1, Marta Alicia Toscano1, Mónica Vermeulen2, Jorge Geffner2, Gabriel Adrian Rabinovich3 1 Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, CONICET. Buenos Aires, Argentina 2 IIHEMA, Academia Nacional de Medicina. Buenos Aires, Argentina Galectin-1, a glycan-binding protein, plays a critical role as a regulator of immune cell homeostasis. Here, we examined the role of endogenous galectin-1 in the regulation of autoimmune inflammation and the physiology of murine dendritic cells (DCs). We found a progressive increase in galectin-1 expression in lymph nodes from animals with MOG35-55- induced experimental autoimmune encephalomyelitis (EAE), which correlated with the pace of the clinical disease (p<0.05). A similar expression profile was observed in CD11c+ DCs purified from spleens at different times of EAE induction (p<0.05). Notably, DCs lacking galectin-1 (Lgals1-/-) had greater immunogenic potential in in vitro and in vivo settings(p<0.05). Consistent with its regulatory function, galectin-1-sufficient DCs isolated from spleens at day 21 of EAE (peak of the disease) and adoptively transferred into Lgals1-/- mice at the day of disease onset successfully restored T-cell tolerance and contributed to the resolution of autoimmune inflammation as reflected by reduced clinical severity, diminished IL-17 and IFN-g production and augmented IL-10 secretion by lymph node cells from Lgals1-/- mice receiving wild-type DCs, compared to Lgals1-/- mice receiving DCs devoid of this protein. We conclude that galectin-1 plays a critical role in limiting the inflammatory response and in fine-tuning the immunogenic function of DCs, thus contributing to disease recovery.