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.

Decidual natural killer cells and the immune microenvironment at the maternal-fetal interface

“…From the foregoing, decidual immune cells form a unique microenvironment, have a dynamic development process in pregnancy, peak in the recasting spiral artery phase, and even reach 30%-40% of all local cells in early pregnancy decidual + phenotype and are endowed with ADCC function (Ni et al, 2013;Li et al, 2015;Wang et al, 2015). pbNK cells also express CD11a and CD11b, forming LFA-1 and MAC-1, respectively, with CD18, which all have ICAM-1 as their corresponding ligand.…”

MicroRNA-708 is downregulated in hepatocellular carcinoma and suppresses tumor invasion and migration

“…There are various factors involved in the development of HCC, 15 including multiple viral infections, chronic inflammation, chronic 16 alcohol abuse and obesity [2]. Surgical resection and liver 17 transplantation are two promising treatment strategies for HCC, 18 however, the clinical outcome of patients remains poor, with a 19 median survival of 6-9 months following diagnosis [3].…”

Activation and Propagation of Tumor-infiltrating Lymphocytes on Clinical-grade Designer Artificial Antigen-presenting Cells for Adoptive Immunotherapy of Melanoma

“…Insulin growth factor-1 (IGF-1), an endocrine mediator of growth and development, was also one of the most up-regulated genes in TIL expanded with aAPC compared to the feeder platform. IGF-1 was reported to be implicated in T-cell differentiation in the thymus as well as NK cell development and cytotoxic function (41, 42). One of the major genes found to be down-regulated in post-aAPC REP TIL was one of the 3 modules that constitutes fibronectin, FN1.…”