Tumor necrosis factor-like weak inducer of apoptosis regulates the phenotype and cytotoxic activity of goat uterine natural killer cells

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) has an important role in the promotion of cell proliferation, migration, and differentiation. However, very little is known about the role of TWEAK in modulating uterine natural killer (uNK) cells' comprehensive functions in ruminants. In the present study, the effects of TWEAK on goat uNK cells were investigated by measuring their cytotoxic function and phenotype as well as cytokine expression in vitro. The results showed that TWEAK protein could be detected in the goat endometrium during estrous cycle and pregnancy. However, a significant increase in ( < 0.05) TWEAK protein levels was observed during very early pregnancy when compared with that during mid pregnancy and later pregnancy as well as during different phases of estrous cycle. Tumor necrosis factor-like weak inducer of apoptosis did not affect proliferation but did decrease ( < 0.05) the cytotoxic activity of uNK cells in vitro. Furthermore, the percentage of CD56/NKp46 uNK cells incubated with TWEAK-containing medium was greater ( < 0.05) compared with those treated with control medium. In addition, uNK cells incubated with TWEAK medium were associated with lesser ( < 0.05) secretion levels and protein expression of interferon-γ (IFN-γ) compared to those incubated with control medium. However, no differences ( > 0.05) could be observed for the secretion levels and protein expression of vascular endothelial growth factor (VEGF) in the uNK cells incubated with TWEAK-containing medium compared with those incubated with control medium. The present preliminary observations indicate that TWEAK has a biological effect on phenotype of uNK cells as well as the secretion and expression of IFN-γ by uNK cells in goats. Moreover, TWEAK decreases the cytotoxicity of goat uNK cells in vitro.