Heterogeneity of IL-15-expressing mesenchymal stromal cells controls natural killer cell development and immune cell homeostasis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE273212 | GEO | 2025/05/16
REPOSITORIES: GEO
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Project description: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. 3 technical replicates each of CD27+ 15a/16-1FKO NK cells, and CD27+ Ctrl NK cells
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