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MicroRNA-15/16 Antagonizes c-Myb to Control Natural Killer Cell Maturation (c-Myb overexpression)


ABSTRACT: NK cells develop in the bone marrow and complete their maturation in peripheral organs, but the molecular events controlling maturation are incompletely understood. Utilizing an NK cell-specific miR-15/16 deficient genetic model (15aKO), we identified a critical role for miR-15/16 family microRNAs in the normal maturation of NK cells in vivo, with a specific reduction in mature CD11b+CD27- NK cells in multiple tissues. The mechanism responsible was a block in differentiation, since accelerated NK cell death was not evident, and earlier intermediates of NK cell maturation were expanded. Further, we identified Myb as a direct target of miR-15/16 in NK cells, with Myb expression increased in immature 15aKO NK cells. Following adoptive transfer, immature 15aKO NK cells exhibited defective maturation, which was rescued by ectopic miR-15/16 expression or Myb knockdown. Moreover, Myb overexpression resulted in defective NK cell maturation. Thus, miR-15/16 regulation of Myb controls the normal NK cell maturation program. KY-1 and KY-2 cell lines overexpressing c-Myb

ORGANISM(S): Mus musculus

SUBMITTER: Todd Fehniger 

PROVIDER: E-GEOD-58268 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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MicroRNA-15/16 Antagonizes Myb To Control NK Cell Maturation.

Sullivan Ryan P RP   Leong Jeffrey W JW   Schneider Stephanie E SE   Ireland Aaron R AR   Berrien-Elliott Melissa M MM   Singh Anvita A   Schappe Timothy T   Jewell Brea A BA   Sexl Veronika V   Fehniger Todd A TA  

Journal of immunology (Baltimore, Md. : 1950) 20150812 6


NK cells develop in the bone marrow and complete their maturation in peripheral organs, but the molecular events controlling maturation are incompletely understood. The miR-15/16 family of microRNA regulates key cellular processes and is abundantly expressed in NK cells. In this study, we identify a critical role for miR-15/16 in the normal maturation of NK cells using a mouse model of NK-specific deletion, in which immature NK cells accumulate in the absence of miR-15/16. The transcription fact  ...[more]

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