关键词: 急性B淋巴细胞白血病, 辅助性T细胞17, IL-17A, 细胞凋亡, 小鼠, 实验研究

Abstract:

Objective To investigate the effect of T helper cell 17（Th17）on the progression of B cell?acute lymphoblastic leukemia （B?ALL）and its possible mechanism. Methods We established the B?ALL mouse model and detected the proportion of Th17 cells in peripheral blood， bone marrow， spleen and lymph nodes by flow cytometry. Further， we used cytokine microarray to analyze the expression of cytokine in peripheral blood of B?ALL mice， and used ELISA to verify the IL?17A expression in peripheral blood of B?ALL mice. Th17 cells were co?cultured with leukemia cells， and the apoptosis ratio of Ki?67 positive cells and B?ALL cells was detected by flow cytometry， the recruitment effect of B?All cells on Th17 cells was analyzed. The expression of apoptosis?related proteins was detected by Western blot. The development of B?ALL by secreting IL-17A from Th17 cells was evaluated in vivo in a mouse model of human acute leukemia. Results Th17 cells were increased in peripheral blood（P < 0.000 1）， bone marrow（P < 0.000 1）， spleen （P < 0.000 1） and lymph nodes （P < 0.000 1） of B?ALL mice. The expression of IL?17A was increased in peripheral blood of B?ALL model mice （P < 0.000 1）， and Th17 cells promoted the proliferation of B?All cells and inhibited their apoptosis through IL?17A （P < 0.000 1）. B?All cells recruit Th17 cells through CXCL16（P < 0.000 1）. The animal experiments showed that IL?17A treatment significantly increased the proportion of leukemia cells in peripheral blood， bone marrow and spleen of B?ALL mice， and shortened their survival time. Conclusion The proportion of Th17 cells in B?ALL increases， B?All cells recruit Th17 cells through CXCL16， and Th17 cells secrete IL-17A to promote B?All progression.

Key words: B cell?acute lymphoblastic leukemia, Th17, IL-17A, cell apoptosis, mice, experimental study