Institute of Immunology, School of Life Sciences, University of Science and Technology of China, 443 Huang-Shan Road, Hefei, Anhui Province 230027, China.
Nat Commun. 2013;4:1479. doi: 10.1038/ncomms2484.
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.
胰岛素样生长因子 1（IGF-1）是许多生理功能的关键调节剂，从长寿到免疫。然而，关于 IGF-1 在自然杀伤细胞发育和功能中的作用知之甚少。在这里，我们确定 IGF-1 在正向调节人类自然杀伤细胞发育和细胞毒性方面的重要作用。具体来说，我们表明人类自然杀伤细胞能够产生 IGF-1，并且内源性 IGF-1 表达的差异导致人类原代自然杀伤细胞的细胞毒性不同。此外，miR-483-3p 被鉴定为自然杀伤细胞中 IGF-1 表达的关键调节因子。miR-483-3p 的过表达类似于 IGF-1 阻断并降低自然杀伤细胞的细胞毒性，而抑制 miR-483-3p 则产生相反的效果，用 IGF-1 中和抗体可逆转这种效果。这些发现表明 IGF-1 和 miR-483-3p 属于一类新的自然杀伤细胞功能调节剂，并加强了 IGF-1 在先天免疫中的突出作用。
