engleski

Galectin-3 deletion modulate NK cell activation

Galectin-3, a β-galactoside binding protein with immune regulatory functions, is overexpressed in a variety of tumor and immune cells in response to various stimuli. Although the expression of Galectin-3 on uterine NK cells (uNK cells) has been suggested to downregulate their function, little is known about the role of Galectin-3 on NK cells, in general. We have observed recently, that Galectin-3-deficient (Gal-3-/-) mice are more resistant to metastatic malignant melanoma. NK cells have been shown critical in reducing tumor lung metastases in melanoma. Objectives: We have investigated the number and phenotype of spleen NK cells in Gal-3-/- and "wild type" (WT) C57BL/6 mice. Methods: We used female Gal-3-/- C57BL/6 and WT C57BL/6 mice, aged 11 weeks. Single-cell suspensions of splenocytes were incubated with mAbs specific for mouse CD3, CD19, NK1.1, CD27, CD11b, and KLRG1, or isotype-matched controls and analised by FACSAria Flow cytometer. Results: Galectin-3-deficient mice have a lower total number of CD3-NK1.1+ cells derived from spleen compared to WT mice (p=0, 008). Despite the reduction in total CD3-NK1.1+, Gal-3-/- mice have a significantly higher percentage of effective cytotoxic and cytokines-producing CD27highCD11bhigh NK cells (p=0, 001) as well as the percentage of immature CD27lowCD11bhigh NK cells (p=0, 004) compared to WT control mice. In contrast, CD27lowCD11bhigh less responsive NK cells were more numerous in Gal-3+/+ mice (p=0, 001). Remarkably, we noticed significantly lower percentage of KLRG1 receptor on NK cells of Gal-3-/- mice as compared to WT control mice (p=0, 002). As KLRG1 is expressed on CD27lowCD11bhigh NK cells, this finding is in accordance with our previous observation. Conclusion: Our data suggest that Galectin-3-deficient mice constitutively have a significantly higher percentage of effective cytotoxic and immature NK cells and this might indicate that gal-3-/- mice display faster turnover of NK cells than WT control mice. These results support our previous findings that lack of Galectin-3 renders mice resistant to lung metastases and enhance innate cytotoxicity in malignant melanoma.

galectin-3; NK cell

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