Abstract
Insulin-like growth factor 1 (IGF-1) is a critical regulator of many physiological functions, ranging from longevity to immunity. However, little is known about the role of IGF-1 in natural killer cell development and function. Here, we identify an essential role for IGF-1 in the positive regulation of human natural killer cell development and cytotoxicity. Specifically, we show that human natural killer cells have the ability to produce IGF-1 and that differential endogenous IGF-1 expression leads to disparate cytotoxicity in human primary natural killer cells. Moreover, miR-483-3p is identified as a critical regulator of IGF-1 expression in natural killer cells. Overexpression of miR-483-3p has an effect similar to IGF-1 blockade and decreased natural killer cell cytotoxicity, whereas inhibition of miR-483-3p has the opposite effect, which is reversible with IGF-1 neutralizing antibody. These findings indicate that IGF-1 and miR-483-3p belong to a new class of natural killer cell functional modulators and strengthen the prominent role of IGF-1 in innate immunity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions / genetics
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Antigens, CD34 / metabolism
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Base Sequence
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Cell Count
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Cell Differentiation / drug effects
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Cell Differentiation / immunology
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Cytotoxicity, Immunologic / drug effects*
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Fetal Blood / cytology
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Flow Cytometry
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Gene Expression Regulation / drug effects
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Gene Knockdown Techniques
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Humans
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Insulin-Like Growth Factor I / genetics
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Insulin-Like Growth Factor I / metabolism
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Insulin-Like Growth Factor I / pharmacology*
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Killer Cells, Natural / cytology*
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Lymphocyte Subsets / cytology
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Lymphocyte Subsets / drug effects
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Lymphocyte Subsets / metabolism
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MicroRNAs / metabolism
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Molecular Sequence Data
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Protein Binding / drug effects
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Protein Binding / genetics
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Subcellular Fractions / drug effects
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Subcellular Fractions / metabolism
Substances
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3' Untranslated Regions
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Antigens, CD34
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MIRN483 microRNA, human
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MicroRNAs
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RNA, Messenger
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Insulin-Like Growth Factor I