MicroRNA-15/16 Antagonizes Myb To Control NK Cell Maturation
Year: 2015
Type: article
Abstract: 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 factor c-Myb (Myb) is expressed preferentially by immature NK cells, is a direct target of miR-15/16, and is increased in 15a/16-1 floxed knockout NK cells. Importantly, maturation of 15a/16-1 floxed knockout NK cells was rescued by Myb knockdown. Moreover, Myb overexpression in wild-type NK cells caused a defective NK cell maturation phenotype similar to deletion of miR-15/16, and Myb overexpression enforces an immature NK cell transcriptional profile. Thus, miR-15/16 regulation of Myb controls the NK cell maturation program.
Source: The Journal of Immunology
Authors: Ryan P Sullivan, Jeffrey W Leong, Stephanie E Schneider, Aaron R Ireland, Melissa M Berrien-Elliott, Anvita Singh, Timothy Schappe, Brea A Jewell, Veronika Sexl, Todd A Fehniger
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: Howard Hughes Medical Institute, Institute of Clinical and Translational Sciences, Alvin J. Siteman Cancer Center, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Advancing Translational Sciences
Awards: Mechanisms underlying cytokine-induced memory-like natural killer cell differentiation and maintenance., Rheumatic Diseases Core Center, Washington University Institute of Clinical and Translational Sciences, MICRORNA REGULATION OF NK CELL DEVELOPMENT AND FUNCTION, Pre-and Postgraduate Training in Molecular Hematology, Cancer Center Support Grant
OpenAlex ID: W2151043904