title: IGF-1 promotes the development and cytotoxic activity of human NK cells.
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.
authors: Institute of Immunology, School of Life Sciences, University of Science and Technology of China, 443 Huang-Shan Road, Hefei, Anhui Province 230027, China.
authors: Fang
authors: F
authors: Ni
authors: Rui
authors: R
authors: Sun
authors: Binqing
authors: B
authors: Fu
authors: Fuyan
authors: F
authors: Wang
authors: Chuang
authors: C
authors: Guo
authors: Zhigang
authors: Z
authors: Tian
authors: Haiming
authors: H
authors: Wei
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D018952:Antigens, CD34 / Q000378:metabolism; D001483:Base Sequence; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D018952:Antigens, CD34; C548912:MIRN483 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I
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