Expression of NK-Activating Receptor-NKp46/NCR1 on NK Cells in Patients with Severe Aplastic Anemia.

BACKGROUND

Severe aplastic anemia (SAA) is a kind of bone marrow failure caused by complex pathogenesis, mainly characterized by severe pancytopenia which causes anemia, hemorrhage, and infection. Natural killer (NK) cells, derived from hematopoietic stem cells (HSCs) or common lymphoid progenitors (CLP), play an important role in the innate immunity and adaptive immune responses. Of the receptors on NK cells, the NKp46/NCR1 is considered to be an important activating receptor for NK cells. However, the quantity and function of NKp46/NCR1 remains unknown.

METHODS

The quantity of NKp46/NCR1 on NK cells in patients with SAA before and after immunosuppressive therapy (IST) was investigated by flow cytometry, quantitative real-time PCR, and western blot. After knockdown of the NKp46/NCR1 gene, NK cells were cultured with K562 cells to detect the function of NK cells.

RESULTS

The results showed that the expression of NKp46/NCR1 in NK cells was significantly higher in untreated SAA patients than those in remission SAA and controls by FCM, qRT-PCR, and WB. After co-culturing with NK cells knockdown with siRNA-NKp46/NCR1, the apoptosis rate of K562 cells was significantly lower compared with the siRNA-scr group and control groups (7.08 ± 5.23% vs. 11.31 ± 7.20% and 10.30 ± 6.08%, p < 0.05).

CONCLUSIONS

We concluded that the decrease of total NK cells and the higher expressions of NKp46/NCR1 on them may be the reason for the hyperfunction of the immune system in SAA patients.