Galectin 1 impair NK cells effector functions

DOMAICA, CAROLINA INÉS; ZIBLAT, ANDREA; RAFFO IRAOLAGOITÍA, XIMENA LUCÍA; SPALLANZANI, RAÚL GERMÁN; CROCI, DIEGO; FUERTES, MERCEDES BEATRIZ; RABINOVICH, GABRIEL ADRIÁN; ZWIRNER, NORBERTO WALTER

Los Cocos

Congreso; 61a Reunión Anual de la Sociedad Argentina de Inmunología,; 2013

Sociedad Argentina de Inmunología

Galectin-1 (Gal-1), an endogenousglycan-binding protein widely expressed at sites of inflammation and by tumor cells, controls a diversity of immune cell processes, acting either extracellularly through binding to specific cell surface glycan structures or intracellularly through pathways that remain largely unexplored. Galectin-3 (Gal-3) modulates innate and adaptive immune responses by controlling cell adhesion, chemotaxis, cytokine secretion and apoptosis. Gal-3 may have positive or negative effects on inflammation depending on tissue and intracellular localization. Natural killer (NK) cells trigger cytotoxicity and interferon (IFN)- g secretion upon engagement of activating receptors by ligands expressed on tumor cells. The objective of this study was to elucidate the effect of Gal-1 and Gal-3 on NK cell effector functions. We first examined the ?glycosylation signature? of resting and cytokine-activated (IL-12/IL-15/IL-18) human NK cells. We found by flow cytometry (FC) that NK cells, independently of their activation status, exhibited cell surface N- glycans that are critical for Gal-1 and Gal-3 signaling, which is consistent with the binding pattern observed for these proteins. When isolated NK cells were activated overnight with IL-12, IL-15 and IL-18 in the absence or in the presence of Gal-1 or Gal-3 and NK cell effector functions were analyzed, we observed by FC with CFSE-labeled target cells and 7-AAD staining that NK cells activated in the presence of Gal-1 showed a significant reduction in the cytotoxicity against K562 cells (p<0,01) whereas Gal-3 did not modulate the NK cell response. Moreover, NK cells activated in the presence of Gal-1 exhibited a lower production of IFN-g than NK cells cultured only in the presence of the cytokines (p<0,05). Inhibition of cytotoxicity and IFN-g secretion was not due to Gal-1 induced NK cell apoptosis. Collectively, our results suggest that Gal-1, but no Gal-3, negatively regulates NK cell effector functions.