FoxO1 controls the expansion of pre-B cells by regulating the expression of interleukin 7 receptor α chain and its signal pathway

Abstract

Forkhead box O1 (FoxO1) has a crucial role in the early B cell development. To understand the functional importance of FoxO1 gene in the early B cell expansion, we established a FoxO1 knockdown model using 70Z/3 pre-B cell line. The FoxO1 knockdown 70Z/3 cells (70Z/3-KD cells) showed the down-regulated expression of interleukin 7 receptor α chain (IL-7Rα). Moreover, the signaling via IL-7Rα was significantly attenuated in the 70Z/3-KD cells, and this alteration was fully rescued by re-expression of FoxO1 gene. Compared to the mock cells, loss of FoxO1 reduced the growth rates in the 70Z/3-KD cells, and was fully rescued by reintroduction of FoxO1 gene. The expansion of pre-B cells (CD45R⁺CD43^- fraction) was also reduced by the knockdown of FoxO1 gene. Indeed, FoxO1 induces accumulation in the p27-mediated G0/G1 phase arrest in 70Z/3 cells. FoxO1 bound to the Il7ra locus specifically and regulate the IL-7Rα transcription. In conclusion, FoxO1 regulates the expansion of pre-B cells by regulating the expression of IL-7Rα and its signal transduction.

Keywords: FoxO1; IL-7Rα; Signal pathway; pre-B cell.