Downregulation of microRNA-24 and-181 parallels the upregulation of IFN-γ secreted by activated human CD4 lymphocytes

IFN-gamma is a cytokine with important roles in the innate and adaptive immune responses. This cytokine is secreted by activated T cells, NK cells and macrophages. Studies on the regulation of human IFN-gamma expression had been previously focused on the promoter region. Consequently, the role of microRNAs (miRs) in this regulation has not been investigated yet. As miR-24 and miR-181 were found to have potential target sites in IFN-gamma mRNA 3'UTR, we assessed their impact on IFN-gamma expression by co-stimulating PB CD4+ T cells with anti-CD3, anti-CD28, IL-12, and IL-18. This co-stimulation cocktail induced an abundant secretion of IFN-gamma together with a down-regulation of miR-24, and miR-181. Existence of a link between these two phenomena was further substantiated by transfection and transduction assays that showed that these two miRs negatively regulate IFN-gamma expression by directly binding to their target sites in the mRNA. Thus, identifying target sites for miR-24 and miR-181 in IFN-gamma-3'UTR points to a novel regulatory mechanism of this crucial gene. (C) 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.