Human NK cell activation triggers galectin 1 secretion which regulates the magnitude of IFN- secretion in a CD45-dependent manner

DOMAICA CI; ZIBLAT A; SECCHIARI F; NUÑEZ SY; TORRES NI; SIERRA JM; IRAOLAGOITIA XL; SPALLANZANI RG; CROCI DO; PEREZ SAEZ JM; FUERTES MB; RABINOVICH GA; ZWIRNER NW

Mar del plata

Congreso; LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2016

SAI

Galectin-1 (Gal-1) is an endogenous glycan-binding protein widely expressed at sites of inflammation and by tumor cells that controls a diversity of immune cell processes through binding to specific cell surface glycan structures or through intracellular ill-defined pathways. Gal-1 binds specifically to the cell surface glycoproteins CD45, CD43 and CD7. Natural killer (NK) cells trigger cytotoxicity and interferon (IFN)- secretion upon engagement of activating receptors by ligands expressed on tumor cells. Previously we demonstrated that Gal-1 negatively regulates NK cell effector functions. The objective of this study was to elucidate the mechanisms involved in the regulation of NK cell effector functions by Gal-1. To further investigate this susceptibility, we analyzed the binding of biotinylated Gal-1 by flow cytometry to NK cells and observed that Gal-1 binds to resting and activated NK cells in a carbohydrate-dependent manner, as the addition of lactose inhibited such binding. NK cells activated with cytokines in the presence of Gal-1 and the PTP CD45 inhibitor exhibited an equivalent production of IFN- than cytokine-activated NK cells. Also, by ELISA we observed that NK cells, independently of their activation status secreted Gal-1, but that activated NK cells exhibited a higher production of Gal-1 than resting NK cells (p