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.

journal_name

Immunol Lett

journal_title

Immunology letters

authors

Li Z,Zhang N,Hui F,Zahid D,Zheng W,Xu X,Li W

doi

10.1016/j.imlet.2019.09.004

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

28-35

eissn

0165-2478

issn

1879-0542

pii

S0165-2478(19)30287-1

journal_volume

216

pub_type

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