| Literature DB >> 25769609 |
Youcai Deng1, Yann Kerdiles2, Jianhong Chu3, Shunzong Yuan4, Youwei Wang3, Xilin Chen4, Hsiaoyin Mao3, Lingling Zhang3, Jianying Zhang5, Tiffany Hughes3, Yafei Deng6, Qi Zhang6, Fangjie Wang6, Xianghong Zou3, Chang-Gong Liu7, Aharon G Freud3, Xiaohui Li6, Michael A Caligiuri8, Eric Vivier9, Jianhua Yu10.
Abstract
Little is known about the role of negative regulators in controlling natural killer (NK) cell development and effector functions. Foxo1 is a multifunctional transcription factor of the forkhead family. Using a mouse model of conditional deletion in NK cells, we found that Foxo1 negatively controlled NK cell differentiation and function. Immature NK cells expressed abundant Foxo1 and little Tbx21 relative to mature NK cells, but these two transcription factors reversed their expression as NK cells proceeded through development. Foxo1 promoted NK cell homing to lymph nodes by upregulating CD62L expression and inhibited late-stage maturation and effector functions by repressing Tbx21 expression. Loss of Foxo1 rescued the defect in late-stage NK cell maturation in heterozygous Tbx21(+/-) mice. Collectively, our data reveal a regulatory pathway by which the negative regulator Foxo1 and the positive regulator Tbx21 play opposing roles in controlling NK cell development and effector functions.Entities:
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Year: 2015 PMID： 25769609 PMCID： PMC4400836 DOI： 10.1016/j.immuni.2015.02.006
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745